Physiology of Hunger
Introduction
Obesity is an imbalance in energy metabolism. At steady state: energy input = energy output.
Energy Input is from ingested CHO, Fat and Protein
Energy Output is from: mechanic work, membrane transport, metabolic conversions, heat production, etc.
For each 9.3 kcals of excess energy, 1 gram of fat is stored.
Remember 9 kcal/gram for fat, only 4 kcal/grams of CHO or protein.
Energy Sources
Glycogen 250-500 grams of stored CHO in 70 kg adult. Enough for 1 day. CHO intake promotes CHO oxidation.
- Glycogen can be expanded by 200-300 grams before fat synthesis is induced. Excess CHOs need to be consumed for several days before the process of de novo lipogenesis occurs at significant rates.
Fat Reserve the body stores 10-25 kg of fat (100,000- 200,000 kcal). Fat intake does not promote fat oxidation. Remember glucose can not be made from fatty acids.
Obesity 1/3rd of North Americans are obese (BMI > 30), if the current trend continues by 2230 100% of US adults will be obese. Obesity signals the presence of one or more of a large collection of disturbances in energy balance.
- Factors contributing to obesity psychogenic, neurogenic, genetic, hormonal, childhood overnutrition (Ý adipocytes)
Energy balance results from the integration of numerous signals that originate from different organ systems and are communicated by a variety of signaling molecules.
- PANCREATIC b CELLS secrete INSULIN. Elevated blood glucose stimulates b cells to synthesize and secrete insulin.
- INSULIN- Peripheral effects (also heart, kidneys, and testes) acts on receptors in adipocytes and muscle to stimulate glucose uptake. Also links the bodys fat mass to satiety signals generated by the brain. Hyperinsulinemia is characteristic of obesity.
- Central Effects
the brain has insulin receptors, insulin itself is in the CSF.
- PANCREATIC a CELLS produce GLUCAGON. Low blood glucose stimulates glucagon synthesis and secretion.
- GLUCAGON acts on receptors in the liver and muscle to stimulate glycogen breakdown.
Adipocytes are central players in signaling between food intake and energy expenditure.
- Adipocytes vary in # and size. Ý # (hyperplasia) occurs during infancy and adolescence. Ý size (hypertrophy) occurs during fat storage. Both hypertrophy and hyperplasia occur in obese patients.
- Hypertrophied adipocytes have ß density of insulin receptors causing insulin resistance. Reversible by weight loss.
Signalling
TNFa a pluripotent cytokine produced by macrophages and adipocytes. TNFa is elevated in obese individuals and is implicated in the development of insulin resistance. (TNFa desensitizes and downregulates the insulin receptors)
LEPTIN the 146 amino acid, soluble hormone, product of the OB gene. (7q31), released by white adipose tissue as a "satiety factor". Contains 4 a helixes. Has a high binding affinity. Obese humans have higher levels of Leptin expression. Leptin uses JAK/STAT upregulation in adipocytes and neurons. Ultimately a nuclear effect; changes gene expression.
- Central Effects -
Acts directly on the ventromedial hypothalamus (the satiety center) where it decreases the synthesis and secretion of neuropeptide Y (NPY), a potent appetite stimulator.
- Peripheral Effects
leptin acts on adipocytes to stimulate lipolysis. Leptin acts on
b cells to inhibit the secretion of insulin.
- However, insulin has a positive effect on leptin secretion. (feedback to control CHO/fat usage)
NEUROPEPTIDE Y a 36 amino acid peptide, levels of NPY go up in times of greatest energy demand or depletion to restore positive energy balance through processes related to CHO intake and metabolism. The ventrolateral hypothalamus receives dense innervation from NPY containing neurons which arise from adrenergic and non-adrenergic cells in the lower brainstem. Localized in the brain, NPY levels are controlled by LEPTIN.
OREXIN Greek, to stimulate appetite, a neuropeptide that triggers G-coupled protein receptors in the ventrolateral hypothalamus (feeding center) to stimulate appetite and food consumption. Two types found in humans so far: orexin A and orexin B.
HYPOTHALAMUS - less than 1% of brain mass. Controls most vegetative (body temp, osmolality, drive to eat and drink, body weight) and endocrine functions as well as many aspects of emotional behavior.
- Ventromedial nuclei the satiety center, without it, marked obesity and hyperphagia (eat a great deal)
- Ventrolateral nuclei the feeding center, without it, absence of food intake, anorexia
Treatment of Obesity
surgery: mechanically restrict the functional stomach or limit the absorbing surface of the jejunum. Drugs: may target energy expenditure, fat synthesis and storage, digestion and absorption of nutrients, and increase the satiating power of foods.
OBJECTIVES OF ANTI-OBESITY TREATMENT - ß body fat, improve compliance to dietary requirements, ß hunger, to avoid tolerance, prevent a ß in metabolic rate, ß intake of dietary fat.