Food intake, adipose tissue, role

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Detailed review of the role of leptin in body-weight regulation, the control of food intake, and the roles of white and brown adipose tissues in energy expenditure. 

Fig. 21.2 Major effects of AMPK activation on numerous tissues. AMPK plays a key role in regulating whole body energy storage and expenditure. In hypothalamus, AMPK is involved in regulation of satiety and food intake. Activation of AMPK in the hypothalamus increases food intake, whereas inhibition decreases intake. In peripheral tissues such as skeletal muscle and liver, activation of AMPK increases energy expenditure by stimulating mitochondrial genesis and energy substrate utilization. AMPK also regulates lipolysis in adipose tissue and insulin secretion in pancreas.

Two organs in the body play a paramount role in regulating food intake the gastrointestinal tract (GIT) and the brain. In addition, the adipose tissue and the islet cells in the pancreas play large part. 

Although most leptin is secreted by adipose tissue, it is also secreted by muscle and the gastric mucosa. The role of leptin secretion by muscle is unclear, but in response to a meal there is a small increase in circulating leptin, presumably from the gastric mucosa. This suggests that, in addition to its role in long-term control of food intake and energy expenditure, leptin may be important in responses to food intake. Insulin (which is secreted mainly in response to food intake section 5.3.1) stimulates the synthesis and secretion of leptin in adipose tissue. 

Leptin (OB proteins) is secreted from adipose tissue and plays a role in body weight homeostasis by regulating food intake and energy expense, and was suggested in the treatment of obesity. An interesting modification method of OB involves a dual PEGylation of a recombinant OB (rOB) where Arg-78 is mutated into Cys-78. The linking of two PEG chains with different reactivity in two different protein sites is therefore possible. First, MAL-PEG... 

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