**3. Maternal hyperlipidaemia of pregnancy**

The enhanced net breakdown of fat depots during late pregnancy is associated with hyperlipidaemia, which chiefly corresponds to plasma rises in TGs with smaller rise in phospholipids and cholesterol [44]. The greatest increased in plasma TGs corresponds to VLDL values but TGs also accumulates in other lipoprotein fractions, which do not normally transport them, such as LDL and HDL [45]. The high TGs concentration secondary to lipolysis in the presence of increased cholesteryl ester transfer protein(CETP) activity, occurring in midgestation[45], contributes to the accumulation of TGs in the lipoprotein fractions of higher densities, LDL and HDL[44, 45]. CETP facilitates the exchange of TGs by esterified cholesterol between VLDL and either LDL or HDL. Furthermore, during late gestation the activity of hepatic lipase (HL) greatly decreased [45]. HL converts the buoyant HDL-2-TG-rich particles into small HDL-3-TG-poor particle allowing a proportional accumulation of buoyant HDL-2-TG-rich particle.

Other hormonal dynamism occurring during pregnancy contributing to maternal hypertriglyceridaemia are, **table** 1, consistently increasing oestrogen concentration almost throughout the gestation period and oestrogen has been shown to (1) increase endogenous production of VLDL-TGs [46]; (2) reduce adipose tissue LPL activity [33, 45], and (3) inhibition of hepatic TG lipase activity [33, 44]. Thus, the oestrogenic influence over TG metabolism suggests an increased circulating VLDL-TG. Although the role of progesterone in TG metabolism is not certain, its administration in rats had a lipid neutral effect. Thus, the interaction between oestrogen and progesterone would favour hypertriglyceridaemia. Prolactin may inhibit adipose tissue LPL while stimulating breast LPL in late gestation [45]. Thus, the physiologic outcome of increasing concentration of Prolactin with advancing pregnancy would be a shift in storage from the adipocytes to the breast in preparation for lactation.

50 Lipoproteins – Role in Health and Diseases

synthesis [43].

is further enhanced [44].

**3. Maternal hyperlipidaemia of pregnancy** 

accumulation of buoyant HDL-2-TG-rich particle.

utilization rates are highest at 22 to 26weeks decreasing near term. In contrast lipid transport is maximal in the 3rd trimester coincident with rapid fetal fat accretion, this spares the mother to utilize glucose during this period. Humans are born with the highest percentage of fat (12 to 15%) compared to any species and 90% deposition occurs in the last 10weeks of gestation, exponentially increasing to 7g/day near term. The preferential use of glycerol released from maternal adipose tissue for gluconeogenesis acquire greater importance during maternal fasting period, when circulating glucose levels are lower than under nonpregnant conditions[34]. Under fed condition in early gestation, plasma ketone body values are even lower in pregnant than in nonpregnant condition [41], indicating an enhanced use of these fuels by maternal tissues as alternative substrate to glucose. However, during fasting period maternal ketogenesis become highly accelerated, as indicated by the exaggerated increase in plasma ketone bodies that occur [41]. This benefit the fetus in two ways: (1) ketone bodies are used by maternal tissues, thus, saving glucose for essential function and delivery to the fetus, (2) placental transfer of ketone bodies is very efficient, attaining the same concentration in fetal plasma as in maternal circulation[42]. In addition, ketone bodies may be used by the fetus as oxidative fuels as well as substrate for brain lipid

Insulin is well known to inhibits adipose tissue lipolytic activity, hepatic gluconeogenesis and ketogenesis but to increases adipose tissue LPL activity. Thus, it is not surprising that all of these pathways change in the opposite direction which is consistent with insulin resistance occurring in later part of pregnancy. These pathways become even further modified under uncontrolled gestational diabetes mellitus(GDM), where insulin resistance

The enhanced net breakdown of fat depots during late pregnancy is associated with hyperlipidaemia, which chiefly corresponds to plasma rises in TGs with smaller rise in phospholipids and cholesterol [44]. The greatest increased in plasma TGs corresponds to VLDL values but TGs also accumulates in other lipoprotein fractions, which do not normally transport them, such as LDL and HDL [45]. The high TGs concentration secondary to lipolysis in the presence of increased cholesteryl ester transfer protein(CETP) activity, occurring in midgestation[45], contributes to the accumulation of TGs in the lipoprotein fractions of higher densities, LDL and HDL[44, 45]. CETP facilitates the exchange of TGs by esterified cholesterol between VLDL and either LDL or HDL. Furthermore, during late gestation the activity of hepatic lipase (HL) greatly decreased [45]. HL converts the buoyant HDL-2-TG-rich particles into small HDL-3-TG-poor particle allowing a proportional

Other hormonal dynamism occurring during pregnancy contributing to maternal hypertriglyceridaemia are, **table** 1, consistently increasing oestrogen concentration almost throughout the gestation period and oestrogen has been shown to (1) increase endogenous production of VLDL-TGs [46]; (2) reduce adipose tissue LPL activity [33, 45], and (3) inhibition


**Table 1.** Hormone and enzyme changes during the course of pregnancy.

The combined effects of enhanced liver production of VLDL [47, 48], decreased removal of these particles from the circulation due to low LPL activity [45,49], high CETP activity and low HL activity, would not only be responsible for the accumulation of TGs in LDL but also for the proportional accumulation of TG in buoyant TG-rich HDL-2b subfractions at the expense of the cholesterol-rich and TG-poor HDL-2a or HDL-3[45].

The increasing insulin-resistance in late gestation and continuously increasing plasma oestrogen levels occurring during pregnancy are the main hormonal factors responsible for these metabolic changes resulting into the development of maternal hypertriglyceridaemia, see table 2.


**Table 2.** The increasing lipid and lipoproteins during course of gestation(courtesy: Ahmet Basaran, MD)
