**3. Results**

sex hormones to suppress lipolysis in adipose tissue regardless of sensitivity to

**Keywords:** lipoprotein metabolism, metabolic syndrome, hamsters, age differences

Metabolic syndrome (MS) is the complex of hormonal and metabolic disorders that increase the risk of type 2 diabetes mellitus and cardiovascular system (CVS) diseases [59, 78]. It was found the close pathogenic link between obesity, hypertension, insulin resistance (IR) and

According to clinical observations, MS was already registered in 20–25% of the adult popula‐ tion of the industrialized countries in 2004 [36, 61]. In epidemiological studies was found that among examined 8814 men and women older than 20 years the incidence of MS according to the US National Cholesterol Education Program (NCEP) criteria was about 24% among men and 25% among women in the USA [5, 6]. In another epidemiological study examining men of all ages, selected by random sampling, MS was diagnosed in 26.2% of the cases [37]. This prevalence of MS in the population increases with age and is highest among the elderly [24, 38]. In the results of other research groups related to the analysis of men and women, conducted in the USA, MS according to NCEP criterion was diagnosed in 6.7% people aged 20–29 years, in 43.5% people aged 60–69 years, and in 42% people aged 70 years [37,38]. It is also known that MS at a younger age is more common in men, but in women the incidence of MS increases

However, gender differences in age-related lipid metabolism changes under MS are not fully understood. In order to investigate the mechanisms of atherogenic dyslipidemia under MS, we study the dynamics of some parameters of lipid and lipoprotein metabolism in hamsters

Experiments were planned to develop a diet-induced MS in Golden Syrian hamsters of different sex and age (4 weeks, 20 weeks, 1 year at the beginning of the experiment), which were kept in a standard vivarium condition. Animals were fed a standard normal diet (intact group), and for 5 weeks a high-calorie diet that contained 29% of fats (predominantly saturat‐ ed) with fructose addition – 1 g daily per 100 g body weight (MS groups) [27, 63]. Blood and liver samples were taken after decapitation in necessary terms and prepared according to

Experiments were carried out according to the "European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes" (Strasbourg, 1985).

atherogenic dyslipidemia in the 60's of the last century [54].

gradually with age – especially during menopause [13, 78].

insulin.

18 Lipoproteins - From Bench to Bedside

**1. Introduction**

of different sex and age.

individual procedures.

**2. Material and methods**

Changes in blood hormone levels observed under the MS led to a shift in the lipolysis/ lipogenesis balance and were accompanied by the excessive production of the free fatty acids (FFA).

According to our data, blood FFA levels in animals fed high-calorie diet were significantly increased in all experimental groups except the young females (Table 1).

Indeed, the FFA level was increased by approximately 40% in male experimental animals independently of age, and in young females this index was practically unchanged, but in the adult it increased also by 40% under experimental pathology. However, even such increased FFA level was 17% lower than in intact males of the same age.


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact group.

**Table 1.** The serum free fatty acids content in male Syrian hamsters with the experimental metabolic syndrome

Our study of lipid and lipoprotein metabolism in the blood serum and liver under modeling MS in Syrian hamsters of different sex and age also indicates the significant changes in lipid metabolism as well as sex and age differences of lipid and lipoprotein metabolism in the health animals and under the experimental MS.


Intact groups – animals fed standard normal diet aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. Each group was composed of six animals.

Mean±S.D. \* – р≤0.05 vs the same age intact group.

**Table 2.** Some indices of lipid metabolism in blood serum of male Syrian hamsters with the experimental metabolic syndrome

Atherogenic dyslipidemia develops independently of age in males fed high-calorie diet (Table 2). As it can be seen from the data presented, increase of total lipids content in the blood serum of animals is mediated by the increase of apoB-LP level because the HDL content did not change. Herewith, the serum TAG level rose by 47% and 30% relative to intact groups in young and adult animals, respectively (Table 2).

**Sex Age Group Free fatty acids content,**

4 weeks

20 weeks

4 weeks

20 weeks

Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals.

Our study of lipid and lipoprotein metabolism in the blood serum and liver under modeling MS in Syrian hamsters of different sex and age also indicates the significant changes in lipid metabolism as well as sex and age differences of lipid and lipoprotein metabolism in the health

> **Total cholesterol, mmol/L**

Intact 1.06±0.07 2.93±0.19 4.72±0.23 1.11±0.05 MS 1.56±0.09\* 3.56±0.10\* 6.68±0.15\* 0.98±0.07

Intact 1.57±0.22 2.84±0.15 5.66±0.34 1.01±0.02 MS 2.00±0.13\* 3.71±0,18\* 6.68±0.21\* 0.85±0.08

Intact 1.50±0.10 2.73±0.02 5.21±0.06 1.74±0.13 MS 2.27±0.13\* 3.15±0.08\* 7.00±0.22\* 2.32±0.13\*

Intact groups – animals fed standard normal diet aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. Each group was composed of

**Table 2.** Some indices of lipid metabolism in blood serum of male Syrian hamsters with the experimental metabolic

**Indices**

**apoВ-containing lipoproteins, g/L**

**High density lipoproteins, g/L**

**Table 1.** The serum free fatty acids content in male Syrian hamsters with the experimental metabolic syndrome

Males

20 Lipoproteins - From Bench to Bedside

Females

Mean±S.D. \* – р≤0.05 vs the same age intact group.

animals and under the experimental MS.

Mean±S.D. \* – р≤0.05 vs the same age intact group.

**Triacylglycerols, g/L**

**Age Group**

4 weeks

20 weeks

1 year

six animals.

syndrome

**mmol/L**

Intact 1.02±0.07 MS 1.44±0.29\*

Intact 1.64±0.16 MS 2.29±0.25\*

Intact 0.91±0.42 MS 0.85±0.03

Intact 0.85±0.04 MS 1.20±0.14\* According to our data the accumulation of apoB-LP in the blood and increasing of these class lipoproteins content in the liver undergo simultaneously (Table 3).


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact group.

**Table 3.** Some indices of lipid metabolism in the liver of male Syrian hamsters with the experimental metabolic syndrome (for the damp tissue)

The significant changes in the lipid and lipoprotein metabolism were observed in the liver of adult male hamsters (1 year old) fed high-calorie diet (Tables 4 and 5). In particular, the changes of apoB-LP composition in the liver (Table 4) led to lipid depletion by lipoproteins.


Intact group – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS group – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment. Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

**Table 4.** The composition of apoB-containing lipoproteins post mitochondrial fraction in liver of the 1-year-old male Syrian hamsters with the experimental metabolic syndrome

The low lipid content, predominantly TAGs, in the hepatic apoB-LP composition observed in our experiments (Table 4) indicated the lipolysis activation through the triacylglycerol lipases action (e.g., HL) under experimental MS.

Herewith, the lipoprotein uptake by the liver under experimental MS, obviously, is enhanced, as the content of the apoB-LP in this organ was increased (Table 5).

The liver G6PDH activity in experimental animals of this age group declined by 35% compared to the intact group (Table 5).

As can be seen from the obtained data, the 6PGD that is less than G6PDH is sensitive to damage by free radicals, retained its activity, and the NADP-dependent malate dehydrogenase activity even increased under experimental MS (Table 5).


Intact group – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS group – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment. Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

**Table 5.** Some indices of lipid metabolism in the liver of 1-year-old male Syrian hamsters with the experimental metabolic syndrome

The lowering HDL-cholesterol level is apparently associated with an increased rate of CE transfer from HDL to apoВ-LP. According to our data, the CE transfer rate from HDL in animals fed high-calorie diet was increased by 166% and 199% relative to young and adult intact animals, respectively (Table 6).

We recorded the decrease of serum LPL activity and increase in HL activity in young males fed high-calorie diet (Table 7). This may be an additional factor for TAG accumulation in the blood and decrease of the HDL-cholesterol level that we observed in our experiments (see Tables 4 and 6).

Some age-related features in the serum lipid profile were found in the healthy male hamsters with aging (from 4 to 20 weeks). Thus, levels of serum FFA (60%), TAGs (48%), and apoB-LP (20%) increased in 4 weeks old intact males, but the HDL level tended to decrease in 4 weeks old intact males with the unchanged total lipid an lipoprotein content in the blood serum. All this testifies that lipidosis develops with aging. Also we found out that in adult males, the free cholesterol and cholesterol ester levels were lower than in young animals (20% and 25%, respectively), and the cholesterol ester transfer rate from HDL in adult animals exceeded this index in young animals 191% (Table 6).

The low lipid content, predominantly TAGs, in the hepatic apoB-LP composition observed in our experiments (Table 4) indicated the lipolysis activation through the triacylglycerol lipases

Herewith, the lipoprotein uptake by the liver under experimental MS, obviously, is enhanced,

The liver G6PDH activity in experimental animals of this age group declined by 35% compared

As can be seen from the obtained data, the 6PGD that is less than G6PDH is sensitive to damage by free radicals, retained its activity, and the NADP-dependent malate dehydrogenase activity

Malate dehydrogenase, nmol NADPH(H+)/min× mg of protein 14.57±0.40 15.09±0.03\*

Intact group – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS group – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment. Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact

The lowering HDL-cholesterol level is apparently associated with an increased rate of CE transfer from HDL to apoВ-LP. According to our data, the CE transfer rate from HDL in animals fed high-calorie diet was increased by 166% and 199% relative to young and adult intact

We recorded the decrease of serum LPL activity and increase in HL activity in young males fed high-calorie diet (Table 7). This may be an additional factor for TAG accumulation in the blood and decrease of the HDL-cholesterol level that we observed in our experiments (see

Some age-related features in the serum lipid profile were found in the healthy male hamsters with aging (from 4 to 20 weeks). Thus, levels of serum FFA (60%), TAGs (48%), and apoB-LP (20%) increased in 4 weeks old intact males, but the HDL level tended to decrease in 4 weeks

**Table 5.** Some indices of lipid metabolism in the liver of 1-year-old male Syrian hamsters with the experimental

apoB-containing lipoproteins, mg/g for the fresh tissue 14.71±0.46 18.92±0.84\*

Total lipids, g/100 g for the fresh tissue 11.36±0.69 14.97±0.75\*

**Group Intact MS**

4.02±0.17 2.62±0.28\*

1.98±0.15 2.20±0.15

as the content of the apoB-LP in this organ was increased (Table 5).

action (e.g., HL) under experimental MS.

even increased under experimental MS (Table 5).

**Indices**

Glucose-6-phosphate dehydrogenase, nmol NADPH(H+)/min× mg of protein

6-phosphogluconate dehydrogenase, nmol NADPH(H+)/min× mg of protein

to the intact group (Table 5).

22 Lipoproteins - From Bench to Bedside

group.

metabolic syndrome

Tables 4 and 6).

animals, respectively (Table 6).


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact group.

**Table 6.** The HDL-cholesterol and HDL-cholesterol esters content, cholesterol esterification rate, and cholesterol esters transfer in blood serum of male Syrian hamsters with experimental metabolic syndrome


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact groups.

**Table 7.** The post-heparin plasma lipase activities in male Syrian hamsters with experimental metabolic syndrome

The atherogenic dyslipidemia development significantly depends on the age in females in contrast to males (Table 8).


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact groups.

**Table 8.** The indices of lipid metabolism in liver homogenate of female Syrian hamsters with experimental metabolic syndrome (for the damp tissue)

In particular, while significant changes in liver apoB-LP content in males was not observed with aging, this index in females increased at growing up in intact animals by 20%, and in animals with experimental MS by 31%. This indicates intensification of liver lipolytic processes in females with aging and may be a manifestation of the lipid metabolism activation that is proved by similar changes in TL content (Table 8).

Moreover, the female liver contains more lipids than male, especially in adulthood – in intact by 22%, while the MS by 24%. This can be explained by the well-known more pronounced effect of estradiol on liver lipid metabolism intensity compared to testosterone.

However, the G6PDH activity in females was significantly higher than in males, especially under MS by 92% in the young ones, and 85% in the adults (Table 8). In addition, this enzyme activity increased with aging. It can also indicate a significant dependence of the liver lipid metabolism rate from hormonal background. As can be seen from the obtained data (Table 9), feeding high-calorie diet did not lead to pronounced atherogenic changes in serum lipid and lipoprotein spectrum in young hamsters-females. The fact that young females had a more favorable serum lipid profile compared to males of the same age group also attracts attention (Tables 9, 10). Thus, the serum total lipid level in young females was 35% lower compared to males, and the total lipoprotein level lower by 32% (in young intact females 4.01±0.31 mg/ml).

Thus, lower serum total lipoprotein level in females may be associated with the decrease of the apoB-LP content (the content of this lipoprotein atherogenic faction was at 39% lower in females compared to males, and the HDL content was similar in animals of both sexes).

As we can see in Tables 9 and 10, in females cholesterol metabolism also was changed in the blood stream, and these changes clearly depended on age: in young females the activity of CE transfer and the cholesterol esterification rate was increased, in the adults was increased only CE transfer, at the same time, the activity of cholesterol esterification rate decreased.

Sex and Age Differences in Lipoprotein Metabolism Proatherogenic Changes under the Experimental Metabolic... http://dx.doi.org/10.5772/60759 25


**Age Group**

24 Lipoproteins - From Bench to Bedside

4 weeks

10 weeks

**Glucose-6-phosphate dehydrogenase, nmol/min×mg of protein**

Mean±S.D. \* – р≤0.05 vs the same age intact groups.

proved by similar changes in TL content (Table 8).

syndrome (for the damp tissue)

**Indices**

Intact 4.72±0.17\* 117.67±4.72 8.87±0.24 1.27±0.08 0.34±0.03 MS 5.38±0.13\* 144.34±5.00\* 10.24±0.25\* 0.65±0.05\* 1.24±0.05\*

Intact 5.15±0.22 137.54±3.91 10.65±0.46 0.89±0.07 0.83±0.04 MS 5.80±0.15 179.22±3.44\* 13.44±0.30\* 0.46±0.06\* 1.33±0.08\*

Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals.

**Table 8.** The indices of lipid metabolism in liver homogenate of female Syrian hamsters with experimental metabolic

In particular, while significant changes in liver apoB-LP content in males was not observed with aging, this index in females increased at growing up in intact animals by 20%, and in animals with experimental MS by 31%. This indicates intensification of liver lipolytic processes in females with aging and may be a manifestation of the lipid metabolism activation that is

Moreover, the female liver contains more lipids than male, especially in adulthood – in intact by 22%, while the MS by 24%. This can be explained by the well-known more pronounced

However, the G6PDH activity in females was significantly higher than in males, especially under MS by 92% in the young ones, and 85% in the adults (Table 8). In addition, this enzyme activity increased with aging. It can also indicate a significant dependence of the liver lipid metabolism rate from hormonal background. As can be seen from the obtained data (Table 9), feeding high-calorie diet did not lead to pronounced atherogenic changes in serum lipid and lipoprotein spectrum in young hamsters-females. The fact that young females had a more favorable serum lipid profile compared to males of the same age group also attracts attention (Tables 9, 10). Thus, the serum total lipid level in young females was 35% lower compared to males, and the total lipoprotein level lower by 32% (in young intact females 4.01±0.31 mg/ml). Thus, lower serum total lipoprotein level in females may be associated with the decrease of the apoB-LP content (the content of this lipoprotein atherogenic faction was at 39% lower in females compared to males, and the HDL content was similar in animals of both sexes).

As we can see in Tables 9 and 10, in females cholesterol metabolism also was changed in the blood stream, and these changes clearly depended on age: in young females the activity of CE transfer and the cholesterol esterification rate was increased, in the adults was increased only

CE transfer, at the same time, the activity of cholesterol esterification rate decreased.

effect of estradiol on liver lipid metabolism intensity compared to testosterone.

**apoB-containing lipoproteins, mg/g**

**HDL, mg/g**

**Lysosomal lipase, nmol/ min×mg of protein**

**Total lipids (TL), mg/g**

> Intact groups – animals fed standard normal diet aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks, 20 weeks, and 1 year at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact groups.

**Table 9.** Some indices of lipid metabolism in blood serum of female Syrian hamsters with experimental metabolic syndrome

Serum TAG level and total cholesterol in young females was lower by 26% and 21% as compared to the corresponding values of these parameters in males, and the HDL-cholesterol in females exceeded the value of this index in males by 32% (Tables 9 and 10).


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact groups.

**Table 10.** The HDL-cholesterol and HDL-cholesterol esters content, the cholesterol etherification activity and cholesterol ester transfer rate in blood serum of female Syrian hamsters with experimental metabolic syndrome

According to our data, the CE transfer rate in young females was 48% less than it was in the serum of males of the same age group (Table 10). The HL activity in intact young females was 28% less in comparison with males (Table 11).


Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals. Mean±S.D. \* – р≤0.05 vs the same age intact groups.

**Table 11.** The post-heparin plasma lipase activities in female Syrian hamsters with experimental metabolic syndrome

However, it is interesting that female hamsters have more favorable (antiatherogenic) initial lipid serum profile than males. Thus, the total lipid content in intact young females was lower than in males by 35%, and it was almost 25% in adults. This index was almost two times lower than in males even with the MS in young females. Only adult females and males with exper‐ imental pathology hardly differed from each other. The same tendency is typical for the total lipoprotein content and TAG level.

The serum cholesterol content increased by 22% in juvenile age and by 31% in male adults with MS. However, the corresponding index in females remained practically unchanged, which confirms the absence of a direct correlation between the MS development and hyper‐ cholesterolemia. At the same time, there were the changes in lipoprotein fractions: in males with the MS the level of apo-B-LP increased (almost by 20% in adulthood), and the HDL content did not change. On the contrary, HDL level with MS decreased by 32% in adult females, and the content of the apoB-LP remained unchanged.

In intact males aged 4–20 weeks under unchanged total serum lipid and lipoprotein content, the levels of following values increased: TAG (by 48%), FFA (by 60%), and apoB-LP (by 19%). However, the HDL level tended to decrease. There were almost the same changes under experimental MS: the TAG level in adult animals with MS was higher by 28% as compared to the young animals with experimental pathology, FFA level – by 59%, HDL level – decreased by 14%, although the level of apoB-LP remained the same (see Tables 1 and 2).

All these data indicate to the hyperlipidemia increase due to age, which is further enhanced by the hyperinsulinemia and IR development. In females these changes were even more pronounced, although not quite so dramatic. In intact females the total lipid content grew with age by 37% (compared with 24% for males), lipoprotein by 32% (although it was lower than 21% for males), TAG by 22% (less than 39% for males), and apoB-LP by 50% (in males it was more than 33%), and the HDL content decreased by 16% (see Tables 1 and 9).

The situation under MS became worse: increase of the TL level in females having MS with aging was 88%, total lipoproteins was 81%, and TAGs was 164%, which was slightly higher than the corresponding indices in males. However, increased apoB-LP content in females with aging under MS was smaller than in the intact animals and 47% less than males in the older age group (see Tables 8 and 9).

**Age Group**

4 weeks

26 Lipoproteins - From Bench to Bedside

20 weeks

Mean±S.D. \* – р≤0.05 vs the same age intact groups.

lipoprotein content and TAG level.

the content of the apoB-LP remained unchanged.

**Indices**

**Hepatic triglyceride lipase (U/ ml)**

**Lipoprotein lipase (U/ml)**

Intact 12±1 37±2 MS 7±1\* 66±7\*

Intact 9±1 47±2 MS 5±2\* 94±6\*

Intact groups – animals fed standard normal diet aged 4 weeks and 20 weeks at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 4 weeks and 20 weeks at the beginning of the experiment. Each group was composed of six animals.

**Table 11.** The post-heparin plasma lipase activities in female Syrian hamsters with experimental metabolic syndrome

However, it is interesting that female hamsters have more favorable (antiatherogenic) initial lipid serum profile than males. Thus, the total lipid content in intact young females was lower than in males by 35%, and it was almost 25% in adults. This index was almost two times lower than in males even with the MS in young females. Only adult females and males with exper‐ imental pathology hardly differed from each other. The same tendency is typical for the total

The serum cholesterol content increased by 22% in juvenile age and by 31% in male adults with MS. However, the corresponding index in females remained practically unchanged, which confirms the absence of a direct correlation between the MS development and hyper‐ cholesterolemia. At the same time, there were the changes in lipoprotein fractions: in males with the MS the level of apo-B-LP increased (almost by 20% in adulthood), and the HDL content did not change. On the contrary, HDL level with MS decreased by 32% in adult females, and

In intact males aged 4–20 weeks under unchanged total serum lipid and lipoprotein content, the levels of following values increased: TAG (by 48%), FFA (by 60%), and apoB-LP (by 19%). However, the HDL level tended to decrease. There were almost the same changes under experimental MS: the TAG level in adult animals with MS was higher by 28% as compared to the young animals with experimental pathology, FFA level – by 59%, HDL level – decreased

All these data indicate to the hyperlipidemia increase due to age, which is further enhanced by the hyperinsulinemia and IR development. In females these changes were even more pronounced, although not quite so dramatic. In intact females the total lipid content grew with age by 37% (compared with 24% for males), lipoprotein by 32% (although it was lower than 21% for males), TAG by 22% (less than 39% for males), and apoB-LP by 50% (in males it was

by 14%, although the level of apoB-LP remained the same (see Tables 1 and 2).

more than 33%), and the HDL content decreased by 16% (see Tables 1 and 9).

For the next series of experiments we used 1-year-old male and female Syrian hamsters that are most likely to MS development and study pathological changes caused by high-calorie diet during 5 weeks in dynamics.

The liver TAG content in the animals fed high-calorie diet increased after 3 days of experiment and remained at a high level in further periods (see Figure 1). The presence of a significant positive correlation between the liver and serum TAG content in the experimental animals (correlation coefficient 0.9) confirms the leading role of the intracellular TAG content increase in the formation of hypertriacylglycerolemia in our experiments.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

**Figure 1.** The liver triglyceride content in male 1-year-old Syrian hamsters under the experimental metabolic syndrome development (mg/g fresh tissue).

Based on our data, the LAL activity, which reflects the lipoproteins absorption intensity from the blood, decreased in the liver of experimental males at the beginning of our experiments, and it did not change significantly in females, and the enzyme activity increase was observed only after 2 weeks (Figure 2).

As can be seen from the data shown in the Figure 3, the G6PDH activity in males was increasing at the beginning of the experiment, probably because of pentose phosphate pathway activa‐ tion, and after that it was decreasing, probably due to the lipid peroxidation (LPO) activation. As for females this rate was not changed significantly during the experiment.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 2.** The liver lysosomal acid lipase activity in male and female hamsters under the experimental metabolic syn‐ drome.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 3.** The liver glucose-6-phosphate dehydrogenase activity in 1-year-old male and female Syrian hamsters under the experimental metabolic syndrome development.

As can be seen from the data obtained (Figure 4), the severe hypertriacylglycerolemia was developing fairly quickly in males fed high-calorie diet during the whole study period. Serum TAG content in the experimental animals increased after 3 days from the beginning of the experiment and reached its maximum value after 3 weeks (197% in regards to intact), and remained at a high level in the subsequent periods (Figure 4).

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 4.** The serum triacylglycerols and apoB-containing lipoproteins content in 1-year-old male Syrian hamsters un‐ der the experimental metabolic syndrome development.

At the same time, according to our data, feeding high-calorie diet increased serum apoB-LP content in experimental animals, but the elevated levels of these lipoprotein fractions was observed at later time periods and was relatively less pronounced in comparison with the increased serum TAG levels (Figure 4).

The serum FFA content in animals also was increased after 3 days of the experiment and was increasing in subsequent periods as well (Figure 5).

In our experiments, the LPL activity was decreased rapidly since 3 days, during all the study periods (Figure 6), which indicates the stable disorders in VLDL utilization, and may be an additional factor that contributes to the hypertriacylglycerolemia development.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

aged 1 year at the beginning of the experiment.

aged 1 year at the beginning of the experiment.

28 Lipoproteins - From Bench to Bedside

drome.

the experimental metabolic syndrome development.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight)

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight)

**Figure 2.** The liver lysosomal acid lipase activity in male and female hamsters under the experimental metabolic syn‐

**Figure 3.** The liver glucose-6-phosphate dehydrogenase activity in 1-year-old male and female Syrian hamsters under

The abnormal cholesterol transport between different subfractions of lipoprotein particles, which leads to the blood atherogenic profile formation, is under discussion. As we have already noted, in our experiments the CE transfer rate was enhanced and this was already observed in the early stages of MS developing (Figure 7). It correlates with the serum TAG content increasing (the correlation coefficient is 0.77) and suggests that changes in apoB-LP morphology is one of the earliest manifestations of MS proatherogenic process.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 5.** The serum free fatty acids content in 1-year-old male Syrian hamsters under the experimental metabolic syn‐ drome development.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 6.** The serum lipoprotein lipase activity in 1-year-old male and female Syrian hamsters under the experimental metabolic syndrome.

Sex and Age Differences in Lipoprotein Metabolism Proatherogenic Changes under the Experimental Metabolic... http://dx.doi.org/10.5772/60759 31

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 7.** The cholesterol ester transfer rate in serum of 1-year-old male and female Syrian hamsters under the experi‐ mental metabolic syndrome development.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

aged 1 year at the beginning of the experiment.

30 Lipoproteins - From Bench to Bedside

aged 1 year at the beginning of the experiment.

metabolic syndrome.

drome development.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight)

**Figure 5.** The serum free fatty acids content in 1-year-old male Syrian hamsters under the experimental metabolic syn‐

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight)

**Figure 6.** The serum lipoprotein lipase activity in 1-year-old male and female Syrian hamsters under the experimental

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 8.** The cholesterol esterification rate in serum of 1-year-old male and female Syrian hamsters under the experi‐ mental metabolic syndrome.

The changes in CE transfer activity can be accompanied by cholesterol metabolism changes in the LP composition. In particular, the HDL-cholesterol esterification rate had already de‐ creased to the second week of the experiment in all investigated animals of this age group (Figure 8). However, the overall CE level in these antiatherogenic lipoproteins was decreased (Tables 5, 6, and 10). And this fact again underlines the significant role in CE transfer activation between different classes of lipoproteins in proatherogenic changes of lipid metabolism under the MS.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 9.** The serum esterified cholesterol content in 1-year-old male and female Syrian hamsters under the experimen‐ tal metabolic syndrome development.

At the same time, the total CE content in the blood of experimental animals was slightly increased (Figure 9), which is the consequence of the overall lipids accumulation in the blood and liver, and may be associated with more active hepatic cholesterol esterification under the growth of FFA absorption by this organ from the blood. It is known that CE along with the TAG is the transport form of FA; therefore, its number increase should lead to the activation of hepatic CE formation.

Compared with changes in cholesterol metabolism and transfer, HL activity was not increased so quickly with just one week since the beginning of the experiment and remains at a high level in subsequent periods (Figure 10).

The opposite tendency in the HDL content changes in animals of different sex also attracts attention (Figure 11): we found out that HDL content reduced in females and increased in males in the last stages of MS development, but, as we already pointed out, it was decreased in animals of both sexes in the beginning of the experiment.

Sex and Age Differences in Lipoprotein Metabolism Proatherogenic Changes under the Experimental Metabolic... http://dx.doi.org/10.5772/60759 33

The changes in CE transfer activity can be accompanied by cholesterol metabolism changes in the LP composition. In particular, the HDL-cholesterol esterification rate had already de‐ creased to the second week of the experiment in all investigated animals of this age group (Figure 8). However, the overall CE level in these antiatherogenic lipoproteins was decreased (Tables 5, 6, and 10). And this fact again underlines the significant role in CE transfer activation between different classes of lipoproteins in proatherogenic changes of lipid metabolism under

Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight)

**Figure 9.** The serum esterified cholesterol content in 1-year-old male and female Syrian hamsters under the experimen‐

At the same time, the total CE content in the blood of experimental animals was slightly increased (Figure 9), which is the consequence of the overall lipids accumulation in the blood and liver, and may be associated with more active hepatic cholesterol esterification under the growth of FFA absorption by this organ from the blood. It is known that CE along with the TAG is the transport form of FA; therefore, its number increase should lead to the activation

Compared with changes in cholesterol metabolism and transfer, HL activity was not increased so quickly with just one week since the beginning of the experiment and remains at a high

The opposite tendency in the HDL content changes in animals of different sex also attracts attention (Figure 11): we found out that HDL content reduced in females and increased in males in the last stages of MS development, but, as we already pointed out, it was decreased

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group.

aged 1 year at the beginning of the experiment.

level in subsequent periods (Figure 10).

in animals of both sexes in the beginning of the experiment.

tal metabolic syndrome development.

of hepatic CE formation.

the MS.

32 Lipoproteins - From Bench to Bedside

**Figure 10.** The serum hepatic triglyceride lipase activity in 1-year-old male and female Syrian hamsters under the ex‐ perimental metabolic syndrome development.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 11.** The serum high-density lipoproteins content in 1-year-old male and female Syrian hamsters under the ex‐ perimental metabolic syndrome development.

Unlike in males, serum TAG content did not change during the first week in females fed highcalorie diet, and the increase of this index values was observed only after 2 weeks from the beginning of the experiment (Figure 12).

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 12.** The serum triacylglycerols and apoB-containing lipoproteins content in 1-year-old female Syrian hamsters under the experimental metabolic syndrome development.

At the same time, in the serum of females fed high-calorie diet the apoB-LP content did not differ from the intact level during the first 4 weeks of the experiment, and after 5 weeks we found out lower values of this index (Figure 12).

Each group was composed of seven animals. Mean±S.D. \* – р≤0.05 vs intact group. Intact groups – animals fed standard normal diet aged 1 year at the beginning of the experiment. MS groups – animals fed during 5 weeks high-calorie diet that contained 29% of fats with fructose addition (1 g daily per 100 g body weight) aged 1 year at the beginning of the experiment.

**Figure 13.** The liver triacylglycerol content in female Syrian hamsters under the experimental metabolic syndrome de‐ velopment.

The hepatic TAG content did not change during the first three weeks of feeding high-calorie diet and after 4 and 5 weeks since the beginning of the experiment, we found increased values of this index relative to intact 55% and 69%, respectively (Figure 13).
