Body Weight regulation depends on a balance between energy intake and energy expenditure. The diagram indicates some of the factors involved.
In adulthood, body weight tends to stay constant within narrow limits in many people, who manage to achieve a balance between energy intake (food) and energy expenditure (exercise).
The sense of satiety, of fullness in the stomach after eating, limits food intake in many people, although it may be over-ridden in people more addicted to food.
The amount of food in the stomach is sensed by afferent nerves that run in the vagus nerve, and these signals are sent to the hypothalamus.
Other signals relating to the amount food intake and its composition reach the hypothalamus by vagal afferents and though hormonal mechanisms.
Separate nuclei in the hypothalamus appear to be responsible of satiety and appetite; satiation occurs after food intake, and appetite is associated with the initiation and continuation of food intake.
Electrical stimulation of some areas of the hypothalamus cause excessive appetite, causing the animal to become obese. Lesions of these areas give rise to loss of appetite and reduction in body weight
The Arcuate nucleus of the anterior hypothalamus contains Neuropeptide Y (NPY), which is a very potent stimulator of feeding behavior.
Electrical stimulation of other areas of the hypothalamus causes eating to stop, and the animal loses weight, sometimes quite drastically. Lesions of these areas cause increased appetite and obesity.
Image source: Physiological Reviews
Hormonal and Neural mechanisms in the regulation of body weight. THe vagus nerve is the major neuronal pathway signalling the amount of food intake and its composition. Cholecystokinin (CCK), Glucagon-Like Peptide-1 (GLP-1) and Pancreatic Polypeptide (PP) provide satiety signals that aresignalled through the vagus nerve. Systemic influences linked to satiety on the hypothalamus include Adiponectin, Insulin, Leptin, Ghrelin, Peptide YY (PYY) and Oxyntomodulin (OXM). Adiponectin and Leptin arise from adipose tissue, and the other peptides are of gastro-intestinal origin including the small intestine, colon and pancreas.
Vagal and Hormonal Feedback to the Hypothalamus
The hypothalamic nuclei concerned with body weight regulation are subject to short term and longer term signals within the body.
Gastric distension plays an important role as a short term signal through vagal afferents, providing a short term signal that the stomach is full.
Cholecystokinin is a peptide hormone released from the duodenum in response to the presence of nutrients in its lumen. It acts locally on vagal nerve endings, and through the circulation on the gall bladder and other structures. This is also a short term signal.
Changes in nutrient levels in the blood also have fairly rapid effects on feeding mechanisms, possibly though changes in glucose or insulin levels. A number of gastrointestinal peptides are also involved in signalling via the vagus nerve: these include Glucagon-Like Peptide-1 (GLP-1), Pancreatic Polypeptide (PP), PYY, Oxyntomodulin and Ghrelin.
Longer term influences include thyroid activity, which regulates the basal metabolic rate, and catecholamines which also increase metabolism.
A hormone produced by adipose tissue, Leptin, provides a feedback related to the amount of adipose tissue in the body (i.e the major variable in body weight), and its activity. This type of feedback clearly operates in the longer term.
Leptin, Adiponectin and Insulin are involved in the longer term regulation of body weight through their action on the hypothalamus.
Image source: courses.washington.edu
This diagram indicated the role of Leptin, the hormone produced by adipose tissue, on the hypothalamus and on feeding behaviour.
Leptin and Neuropeptide Y (NPY)
Leptin is a protein hormone secreted by adipose tissue and has important effects in regulating body weight, metabolism and reproductive function. It acts on the hypothalamic nuclei concerned with the regulation of body weight, and is regarded as a feedback mechanism which lets the hypothalamus monitor the amount of fatty tissue ion the body.
Leptin is secreted when fat is laid down in adipose tissue, and its release is less when the amount of adipose tissue is reduced.
Leptin is coded by the ob gene and is absent in animals with two copies of the gene, i.e. the ob/ob genotype - a situation in which Leptin is deficient.
Leptin inhibits NPY neurones in the arcuate nucleus thus reducing appetite. NPY neurones in the Arcuate nucleus increase appetite, and these neurones become more active when leptin levels fall
Leptin also increases energy expenditure by acting on the dorsomedial hypothalamic and the ventromedial hypothalamic nuclei that regulate sympathetic nerve activity which can increase the activity of brown adipose tissue, and metabolism related to thermoregulation and the cardiovascular function.