Preface

Food intake results in a variety of health problems such as obesity, diabetes, thromboembolic diseases, and cardiovascular diseases. These disorders are collectively known as metabolic syndromes.

This book provides new insights into metabolic syndromes and covers the neural mechanisms of food intake, the relationships between amino acid levels in the blood and brain, food intake and thromboembolism, and the influence of intakes of lipids, ω, and trans fatty acids on cardiovascular diseases.

Minokoshi's paper deals with neural regulation of feeding, which is considered to play a central role in the control of the body's energy balance. Recent studies indicate that neuropeptide Y (NPY)-agoui-related peptide (AgRP) neurons and pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus seem to be the primary and reciprocal regulators of food intake. Minokoshi further discusses that 5'-Adenosine monophosphates regulated protein kinase (AMPK) regulated corticotropin-releasing hormone neurons in the hypothalamus regulate the selection of a more palatable diet.

Nishijyo further revied his works on the neural control of food intake. He suggested that there are two forms of feeding behaviors. One is controlled by the hypothalamus and the lower brain stem, which control the internal environment of the body. The second feeding behavior is that in some environments, organisms can easily ingest foods containing high energy.

Such behaviors are controlled by the emotion/reward system such as the amygdala and nucleus accumbens. He asserted that in modern society there are abundant high calorie foods, thus the homeostasis independent control system easily surpasses the homeostasis-dependent control system, which results in obesity.

Excessive intake of glucose or sucrose is blamed for the current obesity pandemic. An essential amino acid, tryptophan, plays an important role in the regulation of food intake, mood, emotions, and sleep because tryptophan is converted to serotonin and melatonin in the brain. Serotonin inhibits food intake, stabilizes moods, while melatonin is important in sleep. It was shown by Wurtman's group that insulin increases the transportation of tryptophan from the blood to the brain and facilitates the transportation of large neutral amino acids from the blood to muscles.

Takada's paper indicated that an intake of sucrose or glucose decreases plasma levels of essential amino acids. It is thought that such amino acids may be transported from the blood to muscles and tryptophan may be transported to the brain because insulin is secreted upon an increase in plasma levels of glucose. Therefore some glucose intake is needed for muscular integrity and various brain functions.

**II**

**Chapter 9 173**

**Chapter 10 185**

**Chapter 11 199**

Regulatory Functions of α-Amylase in the Small Intestine Other than Starch Digestion: α-Glucosidase Activity, Glucose Absorption, Cell Proliferation,

Metabolic Programming and Nutrition *by Poliana Guiomar de Almeida Brasiel and Sheila Cristina Potente Dutra Luquetti*

Acidosis and Anion Gap *by Md. Masudul Hassan*

and Differentiation *by Kimie Date*

It is well known that high energy food intake results in obesity, which is one of the risk factors for thrombosis. Platelet adhesion at injured endothelial sites may cause thrombosis, and such injuries are often related to high plasma levels of lipids, which are from foods. Recently coagulation factors, such as factor X and tissue factors, have been implicated in causing obesity. So, obesity causes thrombosis and thrombosis cause obesity and further diabetes. These problems were addressed by Goto and Nishikawa.

Obesity is also very important in etiology and the treatment of cancer. Cancer comprises the highest causes of death in developed countries including Japan. Venous thromboembolism is a common and serious complication in cancer patients. The incidence of venous thromboembolism is several fold higher in cancer patients compared to people without cancer. Venous thromboembolism is the second leading cause of death in cancer patients being treated with chemotherapy. Yokoyama indicated that certain foods such as fish, vegetables, and fruit may reduce the risk of venous thromboembolism. Aspirin was proposed to reduce cancer incidence and mortality although there are no supporting studies.

Sugimura reviewed papers in the field of gynecology and indicated that epidemiological studies related obesity to an increase in the risk of venous thromboembolism during pregnancy, puerperium, and postpartum hemorrhage. Recent studies showed that hypertensive disorder of pregnancy (HDP) including preeclampsia and gestational diabetes mellitus (GDM) increases the risk of hypertension and diabetes mellitus later in life. Conversely, maternal malnutrition during pregnancy increases the risk of fetal growth restriction and low birth weight. After birth, these people are at an increased risk of developing hypertension and diabetes mellitus. These data clearly indicate the importance of diet and food intake in normal delivery and child growth.

Koba and Takada studied plasma levels of trans-fatty acids (TFA) in Japan and the USA. TFAs are found naturally in ruminant foods (R-TFA) by biohydrogenation in ruminant animals or industrially produced oils (IPTFA) by partial hydrogenation of vegetable or fish oils. The intake of TFA, mainly IP TFA, is associated with an elevated risk of coronary heart disease (CHD), while some prospective cohort studies showed that R-TFA was associated with a lower risk for sudden cardiac death (SCD). Our case-control study showed that trans-C18:2 isomers (IP-TFA) were significantly higher and palmitelaidic acid (R-TFA) levels were lower in patients with the acute coronary syndrome (ACS) compared to healthy men.

We also compared plasma levels of trans-fatty acids. As expected, plasma levels of long chain ω3 fatty acids (docosahexaenoic and eicosapentaenoic acids DHA and EPA) were higher in Japanese men and ω6 fatty acids (e.g. arachidonic acid, AA) were lower compared with American men. Plasma levels of the major industrially produced trans-fatty acids (IP-TFA, elaidic acid, and linoelaidic acid) were far higher in American men. Levels of potentially cardioprotective, primarily ruminant derived trans-fatty acid, palmitelaidic acid, were higher in Japanese men.

These results indicate that outcomes of different food intakes sometimes depend upon various environmental and cultural factors.

Metabolic programming and nutrition are investigated by Poliana Guiomar de Almeida Brasiel and Sheila Cristina Potente Dutra Luquetti

**V**

Md. Masudul Hassan provides us with an insight to acidosis and anion gap, and the book ends with an interesting chapter "*Regulatory Functions of α-Amylase in the Small Intestine Other than Starch Digestion: α-Glucosidase Activity, Glucose Absorption,* 

**Akikazu Takada**

Japan

Japan

Professor Emeritus of Hamamatsu University,

Chairman of NPO "International Projects on Food and Health",

*Cell Proliferation, and Differentiation*" by Kimie Date.

Md. Masudul Hassan provides us with an insight to acidosis and anion gap, and the book ends with an interesting chapter "*Regulatory Functions of α-Amylase in the Small Intestine Other than Starch Digestion: α-Glucosidase Activity, Glucose Absorption, Cell Proliferation, and Differentiation*" by Kimie Date.

> **Akikazu Takada** Professor Emeritus of Hamamatsu University, Japan Chairman of NPO "International Projects on Food and Health", Japan

**IV**

It is well known that high energy food intake results in obesity, which is one of the risk factors for thrombosis. Platelet adhesion at injured endothelial sites may cause thrombosis, and such injuries are often related to high plasma levels of lipids, which are from foods. Recently coagulation factors, such as factor X and tissue factors, have been implicated in causing obesity. So, obesity causes thrombosis and thrombosis cause obesity and further diabetes. These problems were addressed by

Obesity is also very important in etiology and the treatment of cancer. Cancer comprises the highest causes of death in developed countries including Japan. Venous thromboembolism is a common and serious complication in cancer patients. The incidence of venous thromboembolism is several fold higher in cancer patients compared to people without cancer. Venous thromboembolism is the second leading cause of death in cancer patients being treated with chemotherapy. Yokoyama indicated that certain foods such as fish, vegetables, and fruit may reduce the risk of venous thromboembolism. Aspirin was proposed to reduce cancer incidence and

Sugimura reviewed papers in the field of gynecology and indicated that epidemiological studies related obesity to an increase in the risk of venous thromboembolism during pregnancy, puerperium, and postpartum hemorrhage. Recent studies showed that hypertensive disorder of pregnancy (HDP) including preeclampsia and gestational diabetes mellitus (GDM) increases the risk of hypertension and diabetes mellitus later in life. Conversely, maternal malnutrition during pregnancy increases the risk of fetal growth restriction and low birth weight. After birth, these people are at an increased risk of developing hypertension and diabetes mellitus. These data clearly indicate the importance of diet and food intake in normal

Koba and Takada studied plasma levels of trans-fatty acids (TFA) in Japan and the USA. TFAs are found naturally in ruminant foods (R-TFA) by biohydrogenation in ruminant animals or industrially produced oils (IPTFA) by partial hydrogenation of vegetable or fish oils. The intake of TFA, mainly IP TFA, is associated with an elevated risk of coronary heart disease (CHD), while some prospective cohort studies showed that R-TFA was associated with a lower risk for sudden cardiac death (SCD). Our case-control study showed that trans-C18:2 isomers (IP-TFA) were significantly higher and palmitelaidic acid (R-TFA) levels were lower in patients

We also compared plasma levels of trans-fatty acids. As expected, plasma levels of long chain ω3 fatty acids (docosahexaenoic and eicosapentaenoic acids DHA and EPA) were higher in Japanese men and ω6 fatty acids (e.g. arachidonic acid, AA) were lower compared with American men. Plasma levels of the major industrially produced trans-fatty acids (IP-TFA, elaidic acid, and linoelaidic acid) were far higher in American men. Levels of potentially cardioprotective, primarily ruminant

with the acute coronary syndrome (ACS) compared to healthy men.

derived trans-fatty acid, palmitelaidic acid, were higher in Japanese men.

upon various environmental and cultural factors.

Almeida Brasiel and Sheila Cristina Potente Dutra Luquetti

These results indicate that outcomes of different food intakes sometimes depend

Metabolic programming and nutrition are investigated by Poliana Guiomar de

mortality although there are no supporting studies.

Goto and Nishikawa.

delivery and child growth.

**1**

**Chapter 1**

**Abstract**

*Yasuhiko Minokoshi*

macronutrient intake.

**1. Introduction**

macronutrient, carbohydrate selection

regulation of homeostatic and hedonic feeding [2, 3].

Neural Control of Homeostatic

Neural regulation of feeding is key to the control of body energy balance. Recent

studies have identified multiple neural circuits that contribute to the control of homeostatic or hedonic feeding, with these circuits acting cooperatively to regulate feeding overall. Neuropeptide Y (NPY)-agouti-related peptide (AgRP) neurons and pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus appear to be primary and reciprocal regulators of homeostatic food intake. However, the central mechanisms underlying the regulation of nutrient intake remain largely unknown. 5′-Adenosine monophosphate-activated protein kinase (AMPK) is an important molecule in the regulation of energy metabolism. We recently showed that AMPK-regulated corticotrophin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus regulate the selection of carbohydrate over a more palatable diet. Here, I address key recent findings that have shed light on the homeostatic regulation of feeding including total calorie and

**Keywords:** homeostatic feeding, hedonic feeding, hypothalamus, AMPK,

Feeding is one of the most important motivated behaviors for maintenance of body energy balance. Although obesity has become a pandemic in the modern world, young individuals are able to maintain their body weight over a long period, suggesting that body energy balance, at least at a young age, is precisely regulated. Regulation of feeding is generally divided into homeostatic and nonhomeostatic mechanisms [1]. The hypothalamus and brain stem play important roles in homeostatic regulation (**Figure 1**). Nonhomeostatic regulation relates to "hedonic" feeding that manifests as hyperphagia for palatable diets rather than to the control of body energy balance. The reward system including dopaminergic neurons in the ventral tegmental area is associated with hedonic feeding. Homeostatic and nonhomeostatic systems are coordinately regulated under physiological and pathological conditions. The recent introduction of new technologies including optogenetic and pharmacogenetic methods has led to the identification of neural circuits for the regulation of homeostatic feeding in the hypothalamus and other brain areas. In addition to hormones such as leptin, ghrelin, cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1), less well-known hormones such as asprosin and growth and differentiation factor 15 (GDF15) have also recently been implicated in the central

Feeding and Food Selection
