Nutritional Biochemistry

From the Classroom to the Research Bench

Sami Dridi

• Publisher: Bentham Science Publishers
• Year: 2022
• Print ISBN: 9789815051599
• eBook ISBN: 9789815051575
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Nutritional Biochemistry: From the Classroom to the Research Bench aims to provide students and readers with a detailed, simplified, and comprehensive account of the relationship between nutrition and metabolism. A key feature of this textbook is a comparative approach on the subject of nutritional biochemistry which helps to explain the differences in metabolism, nutrient requirement, and sometimes in the molecular pathways between mammalian and non-mammalian species. Chapters give an overview of the need of food and water (chapter 1), before describing the cell and organ system components (chapter 2). The textbook then focuses on the regulation of food intake from the factors influencing appetite to the central and peripheral underlying mechanisms (chapters 3-5). Water intake and regulation in the body are covered (chapter 6), along with key topics of protein, carbohydrate, and lipid metabolism (chapters 7, 8, and 9), including their digestion, absorption, transport, utilization, synthesis, degradation, and molecular regulation. A brief summary concludes the book (Chapter 10). This book serves as a textbook for students and faculty in beginner courses in biochemistry and nutrition and is designed to give learners a comprehensive understanding of the topic to help them when considering a career in research.

Regulation of Food Intake: Central Mechanisms

Sami Dridi

Abstract

Food intake is regulated by complex hypothalamic neuronal systems originally identified as hunger and satiety centers. The search for the underlying mechanisms led to the discovery of several central orexigenic and anorexigenic peptides. The present chapter summarizes the current knowledge about the role of classical hypothalamic neuropeptides such NPY/AgRP, POMC/CART, melanocortin, and orexin system, as well as several new central signals such as AMPK, ncRNA, and autophagy involved in the regulation of appetite and food intake.

Keywords: Hypothalamus, central signals, hunger center, satiety center, orexigenic neuropeptides, anorexigenic neuropeptides, ncRNA, autophagy.

Introduction

Feed intake regulation is highly conserved across animals, and a series of highly integrated regulatory and neuronal mechanisms are involved. Brain lesioning and stimulation studies performed several decades ago involved the hypothalamus as a major site controlling feed intake and body weight. Early researchers found that lesions of the ventromedial hypothalamus (VMH) resulted in hyperphagia¹ and thereby defined it as the “satiety center” [1, 2], while lesions of the lateral hypothalamus area (LHA) resulted in aphagia² and thereby it was termed “hunger center” [3]. As in mammals, lesioning VMH of avian species increased feed intake, whereas lesioning LHA decreased feed intake [4]. As our knowledge of specific neuronal subpopulations involved in the regulation of feed intake has expanded, the term of brain “center” has been replaced by that of discrete neuronal pathways that generated responses to afferent inputs related to changing body fuel stores [5].

4.1. Classical Central Effector Pathways

The hypothalamus contains multiple neuronal systems essential in the regulation of feed intake. Stimulation of some of these systems results in a net increase in energy intake and storage and is thereby referred to as anabolic or orexigenic³ systems. However, for others (catabolic or anorexigenic⁴), stimulation triggers a

net decrease in feed intake and storage. In general, these classical hypothalamic effectors act similarly between mammals and avian species; however, there are notable exceptions (Table 4.1).

4.1.1. NPY/AgRP and POMC/CART Neuropeptides

Two separate populations of neuronal cell types are located in the mammalian arcuate nucleus (ARC, equivalent of infundibular nucleus in avian species); one synthesizes the powerfully orexigenic peptides (neuropeptide Y, NPY and agouti-related peptide, AgRP), while the other produces the anorexigenic pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) [5] (Fig. 4.1). In both mammals and avian species, NPY is one of the most potent appetite stimulators. Central administration of NPY increases energy intake, decreases energy expenditure, and enhances adipogenesis and lipogenesis (de novo fatty acid synthesis, see chapter 9, section 9.4) [6^-9]. Repeated central NPY administration induces obesity within a matter of days [10]. The effects of NPY on feed intake are mainly mediated via NPY receptor 2 (NPY Y2) and 5 (NPY Y5) [11], which belong to G-protein coupled receptors. The search for the underlying mechanism for the agouti obesity syndrome, in part led to the discovery of an endogenous melanocortin receptor (MCR) antagonist, AgRP. AgRP is co-expressed with NPY in the ARC, and when it is released from its neurons, it binds to MC3R and MC4R and, in turn, induces feed intake. Transgenic overexpression of AgRP produces an obesity syndrome [84]. Similarly, genetic deficiency of the MC4R in mice results in hyperphagia and obesity [85]. Unlike rodent models where prolonged effects of AgRP on feed intake have been reported [86], the effects of AgRP in sheep were not apparent after 24h. In pigs, neither AgRP nor SHU9119 (MC4-R antagonist) had any effects on feed intake thought to be due to a mutation in the MC4-R [87]. The expression and activity of NPY and AgRP are increased in conditions associated with weight loss, such as caloric restriction, lactation, and intense exercise [88^-90] of particular interest among central catabolic systems are the melanocortins, neurotransmitters cleaved from the POMC precursor polypeptide. Mice lacking POMC are obese [91] and mutations that cause loss of POMC function in humans produce obesity and insulin resistance [92]. The alpha-melanocyte stimulating hormone (α-MSH), POMC-derived neuropeptide, is an endogenous MCR agonist that reduces feed intake when it acts on MC3R and MC4R [93]. Chronic infusion of α-MSH in the third cerebral ventricle of rats reduced feed intake and body weight [94]. Similarly, central administration of α-MSH suppresses feed intake in chickens [95]. In mammals, β-MSH binds MC4R with higher affinity than α-MSH, however, the opposite (α-MSH has a higher affinity to MC4R than does β-MSH) occurs in chicken [96, 97].

Table 4.1 Comparison of neuropeptide effects on feeding behavior in mammalian and avian species.

(An)Orexigenic Peptides	Avian Species	Mammalian Species
Pancreatic Peptides
NPY	+ [7, 12-16]	+ [46-49]
PP	+ [17]	- [50, 51]
Peptide YY	+ [7]	- [52, 53]
Other Peptides
AgRP	+ [18]	+ [54]
Galanin	+ [19]	+ [55]
Somatostatin	+ [20]	+ [56]
CGRP	- [21]	- [57]
CART	- [22]	- [58]
NPFF	- [23]	- [59]
NPK	- [24]	- [60]
NPS	-	- [61]
Mesotocin	- [25]	- [62]
Substance P	- [26]	- [63]
Vasotocin	- [12]	- [64]
RFamide Peptides
GnIH	+ [27]	+ [65]
26RFa	+ [28]	+ [66]
PrRP	+ [29]	- [67]
Melanocortins
ACTH	- [30]	- [68]
Α-MSH	- [31]	- [69]
CRF Family
CRH	- [32]	+ [70]
Urotensin 1	- [33]	+ [71]
Urocortin	- [34]	+ [72]
Stresscopin	- [35]	+ [73]
Glucagon Family
GLP-1/2	- [36]	- [74, 75]
Oxyntomodulin	- [37]	- [76]
GHRH	- [38]	+ [77]
Brain-gut Peptide
CCK	- [39]	- [78]
Gastrin	- [40]	- [79]
GRP	- [41]	- [80]
Neuromedin B/C/S/U	- [42]	- [81]
Opioid Family
Β-endorphin	+ [43]	+ [82]
Endomorphin-2	+ [44]	+ [44]
Nociceptin	+ [45]	+ [83]

ACTH, adrenocorticotropic hormone; AgRP, agouti related peptide; α-MSH, alpha-melanocyte stimulating hormone; CART, cocaine-amphetamine-regulated transcript; CCK, cholecystokinin; CGRP, calcitonin gene-related peptide; CRH, corticotropin-releasing hormone; GHRH, growth hormone releasing hormone; GLP1/2, glucagon-like peptide1/2; GnIH, gonadotropin-inhibiting hormone; GRP, gastrin-releasing peptide; NPFF, neuropeptide FF; NPS, neuropeptide S; NPY, neuropeptide ...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• INTRODUCTION
• DEDICATION
• Setting the Stage: The Need of Water and Food
• The Cell: The Basic Functional Unit of Life
• Food Intake Regulation: Factors Influencing Food Intake
• Regulation of Food Intake: Central Mechanisms
• Regulation of Food Intake: Peripheral Mechanisms
• Body Fluid Homeostasis and Water Intake Regulation
• Proteins, Amino Acids, and Nitrogen Metabolism
• Carbohydrate Metabolism
• Lipid Metabolism
• Summary