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FOOD INTAKE AND APPETITE CONTROL OF FOOD INTAKE AND APPETITE

What’s the underlying cause? Fast forward 15 years to 2030 Humans are sicker than ever Life expectancy has decreased and productivity is down What’s the underlying cause? Obesity

Traditionally, a distinction has been made between homeostatic & nonhomeostatic control of appetite and food intake

Deviation from homeostatic control physiologic nonphysiologic obesity

CENTRAL CONTROLS OF FOOD INTAKE AND APPETITE Coordination by the Hypothalamus

The hypothalamus is widely recognized as the in the control of food intake and appetite “gate keeper”

the lateral hypothalamus as the “hunger center” and the medial hypothalamus as the “satiety center”

A network of communication among the gut, pancreas, adipose tissue, brainstem, and hypothalamus is well established

Additionally, further communication exists between the hypothalamus and higher cortical centers pertaining to food memory of food, with resulting overall coordinated control of food intake

Role of the Brainstem is the main organ responsible for facilitating the communication between peripheral signals of food intake and hypothalamic nuclei

The arcuate nucleus (ARC) is thought to be the main hypothalamic area controlling food intake

Within the ARC, two groups of neurons are pivotal in regulating food intake One group of neurons contains neuropeptide Y (NPY), and most of these also contain Agouti-related peptide (AgRP) The second group is formed by neurons containing pro-opiomelanocortin (POMC) Activation of these neurons enhances food ntake (orexigenic) Activation of these neurons reduces food intake (anorexigenic)

NPY is the most powerful central stimulant of appetite

Neuropeptides Implicated in the Control of Food Intake Agouti-Related Peptide Cocaine- and Amphetamine-Regulated Transcript Hypothalamic Releasing Hormones Orexins Melanin-Concentrating Hormone Brain-Derived Neurotrophic Factor Ciliary Neurotrophic Factor Central Neurotransmitters

PERIPHERAL CONTROLS OF FOOD INTAKE AND APPETITE Nutrient, hormonal signals from the gastrointestinal system, endocrine organs, and adipose tissue all have essential roles in influencing food intake and appetite

hunger (orexigenic signals) These peripheral signals target areas of the hypothalamus to regulate appetite They include signals conveying a feeling of fullness (satiety signals) and hunger (orexigenic signals)

These signals can control meal size & meal number

Orosensory and Optic Stimuli Neural Signals Orosensory and Optic Stimuli Orosensory and optic stimuli provide the brain with sensory information regarding the nature of food These stimuli include appearance, taste, smell, and textural stimuli

to continue or to stop eating The information is used by the brain to decision to eat or not eat to continue or to stop eating

Gastric Distention Volume-related postprandial gastric distention results in satiety during a meal bariatric surgical

Nutrient Signals Most nutrient signals exert their effects on the gastrointestinal system and the brain and induce the secretion of gastrointestinal hormones and appetite regulation

Gut Hormones the largest endocrine organ secretes more than 30 different regulatory peptide hormones • digestion and absorption • affect short-term feelings of hunger and satiety

These hormones are the subject of extensive research, given their potential as physiologic antiobesity therapies

Cholecystokinin (CCK) It is released postprandially slowed gastric emptying CCK reduces food intake

Ghrelin Increases appetite “hunger hormone” considered as one of the most powerful physiologic orexigenic agents increases food intake and body weight in rodents Plasma ghrelin levels are also noted to increase on weight loss (regain weight )

Peptide YY (PYY) released postprandially PYY administration decreases food intake Obese patients demonstrate a blunted postprandial rise in PYY PYY-based antiobesity agents are currently under development

Glucagon-like Peptide-1(GLP-1) reduces food intake released postprandially reduces gastric emptying analogs of GLP-1 are used in the treatment of type 2 diabetes currently undergoing clinical trials for the treatment of obesity

Pancreatic Hormones major function is to control glucose homeostasis (Insulin & Glucagon) pancreatic polypeptide and amylin, also affect appetite ( are satiety signal and reduces food intake)

Hormones from Adipose Tissue (leptin) a circulating protein produced by adipocytes (fat cells) is a signal from the adipose tissue to the brain that reflects the state of energy stores increased by overfeeding absence of leptin lead to severe obesity Leptin acts on ARC LepR to stimulate POMC neurons and inhibit NPY/AgRP neurons to decrease food intake

Other Hormones Thyroid hormones, gonadal steroids and glucocorticoids regulate metabolic rate, reproductive state and stress responses, respectively These processes rely on adequate energy supplies. Therefore, it is not surprising that hormones regulating these processes are also involved in the endocrine regulation of appetite

Signals from the Immune System Anorexia or decreased food intake during infectious, inflammatory, and neoplastic disease states is very evident. Anorexia appears to result from the action of cytokines in the brain

The word “hedonic” relates to pleasant (or unpleasant) sensations Hedonic Mechanisms The word “hedonic” relates to pleasant (or unpleasant) sensations visual, smell, and taste signals can override satiety signals to maintain food intake

CONCLUSION The regulation of food intake and appetite occurs through the integration of various central and peripheral signals

of food, and numerous environmental and emotional factors These signals interact at the level of the brainstem and hypothalamus to produce an overall response of hunger or fullness Additionally, these neuronal networks are hugely modified by other influences such as sensory inputs, food memory, rewarding aspects of food, and numerous environmental and emotional factors

This modification is a particular feature of modern human eating behavior and may underpin the dysregulation of energy balance that is responsible for the current obesity epidemic

By means of ever-expanding current research , it is hoped that our understanding of the complex and intricate signaling pathways governing appetite control will improve and pave the way for better antiobesity drug treatments

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