chapter 22
Metabolic Homeostasis
and development. If there is a net excess energy intake,
BMI increases, eventually leading to overweight and ul-
timately to obesity and morbid obesity. In a population
with stable genetic factors, increase in obesity is primar-
ily attributable to consumption of excess foods with high
fat content and decreased physical activity. Obesity is a
worldwide health problem. It is a risk factor for devel-
opment of diabetes mellitus, hypertension, and heart dis-
ease, all of which cause decreased quality of life and life
Feeding behavior and energy balance are regulated by
a complex set of short-term and long-term physiological
signals. Mechanisms that lead to obesity involve interac-
tions between genetic, environmental, and neuroendocrine
factors. The short-term regulators of hunger and satiety
may include plasma levels of glucose and amino acids,
cholecystokinin and other hormones, and body tempera-
ture. One of the long-term regulators of food intake and
energy expenditure is an adipocyte-derived hormone lep-
tin (Chapter 5). Leptin is a polypeptide of 167-amino acid
residues that functions in the afferent signal pathway of a
negative feedback loop in regulating the size of adipose
tissue and energy balance. The physiological role of lep-
tin was established by using
mice that
have identical phenotypes of obesity and diabetes mellitus.
In the
mice, leptin levels are low due to mutations
in the leptin gene, and in the
mice the leptin re-
ceptors are defective due to inactivating mutations. The
role of leptin and its receptor was investigated by joining
the circulatory systems (parabiosis) of
mice. In
mice, obesity, diabetes, and sterility are
corrected by leptin administration. These animal studies
have led to understanding of several aspects of obesity in
In humans, leptin is secreted in a pulsatile manner,
in a nyctohemeral rhythm, and in proportion to size
of the adipose tissue. The pathway of leptin’s action
involves the neuroendocrine system of the hypothala-
mus (Figure 22-27). When leptin levels are low, ap-
petite increases via the activation of the neuropeptide Y
Phosphorylated PPARy2
F I G U R E 2 2 - 2 7
A model for the regulation of human food consumption. Asterisks (*) indicate obesity-causing mutations. Abbreviations
are given in the text.
previous page 548 Bhagavan Medical Biochemistry 2001 read online next page 550 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off