Fat Overweight HDL Diabetes Hypertension Depression

Caloric value BMI Overeating Insulin Resistance

Hormonal Regulation in OBESITY

Contents

• Definition• Energy Homeostasis • Adipose tissue as endocrine gland• Hypothalamus as Regulator• Brief Discussion of Different hormones in

relation to appetite control and Obesity• Evolutionary point of view of Obesity

Im I Obesse

• Definition: convention for adults, grade 1 overweight (commonly and simply called overweight) is a BMI of 25-29.9 kg/m2. Grade 2 overweight (commonly called obesity) is a BMI of 30-39.9 kg/m2. Grade 3 overweight (commonly called severe or morbid obesity) is a BMI greater than or equal to 40 kg/m2. - By WHO

• BMI = weight/height2

• body fat percentage = 1.2(BMI) + 0.23(age) - 10.8(sex) - 5.4• Obesity represents a state of excess storage of body fat

• men have a body fat percentage of 15-20%, women have approximately 25-30%

Adipose Tissue

• Adipose tissue or body fat or just fat is loose connective tissue composed mostly of adipocytes. It also contains pre-adipocytes, fibroblasts, vascular endothelial cells and variety of immune cells.

• Role:  to store energy in the form of lipids(triglycerides), although it also cushions and insulates the body.

•  major endocrine organ, as it produces hormones such as leptin, estrogen, resistin,Adiponectin and the cytokine TNFα.

•  types: WAT and BAT

Hypothalamic control of energy Homeostasis

• The arcuate nucleus of the hypothalamus (ARC) contains receptors for leptin, insulin, various peptides and integrate metabolic information they provide through other hypothalamic as well as extra hypothalamic areas

• Utilizing a network of neuropeptides and neurotransmitters, the ARC relays this information to 2nd order hypothalamic sites such as PVN, LHA, DMN, VMN

• Mechanisms utilized by Hypothalamus to appropriately modulate energy balance:

1. Control of appetite

2. Endocrine modulation of thermogenesis

3. Autonomic modulation of energy expenditure

Feedback loop to regulate Energy Balance

Insulin and Leptin as Adiposity Signals

• Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central in regulating carbohydrate & fat metabolism in the body

• Leptin is a 16-kDa Adipose derived hormone that plays a key role in regulating energy intake and energy expenditure, including appetite/hunger & metabolism

• Circulate in proportion to Body Fat Stores• Activate Catabolic circuits suppress anabolic circuits

when their levels are increased resulting in reduced food intake, Increased energy Expenditure and restoration of body Adipose stores.

Role in Controlling Appetite

Other factors in regulating Appetite and Body weight

• Ghrelin:  a 28 amino acid hunger-stimulating peptide and hormone that is produced mainly by P/D1 cells lining the human stomach. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin. It increases expression of NPY.

• Opioids: Increases food intake. Naloxone injection, the Opioid antagonist reduced food intake. A good target for drug development.

• Melanocortins: Control BAT Thermogenesis, Induce Lipolysis in WAT

What happens in Obesity?

• In Normal person:

Insulin & Leptin

POMC MSH Decrease in food IntakeIncreased Energy Expenditure, Loss of FAT

InhibitNPY & AGRP Neurons

But In Most Obese Humans, this setting is exactly the same all the time, Blood Leptin levels always remain high and Represents Resistance to the action of Adiposity signals in Hypothalamus

Inhibit

Obesity and Concordance with Diabetes

• Obesity is generally associated with Insulin de-sensitivity and thereby promote diabetes type 2 disease. This is due to IRS- PIK3 signaling.

• Involve accumulation of Long chain fatty acyl CoA (LCFA). They act to dampen insulin signal transduction by Serin/Threonine Phosphorylation of target insulin receptor and IRS Proteins, molecules normally activated by Tyrosine Phosphorylation.

Is Obesity a Disease?• The Thrifty Genotype Concept

• Neurobiology of Obesity by Jenni Harvey

• Larsen: Williams Textbook of Endocrinology

• WWW.Wikipedia.org• Obesity by Debashish Bagchi

References

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