Peripheral/endocrine signals interact with hypothalamic circuits to control moti

Question

Peripheral/endocrine signals interact with hypothalamic circuits to control motivated behavior. In particular, the roles of specific populations of neurons within the hypothalamus regulate feeding and metabolic activity. The action of hormones on these neurons is also well known.

Describe the effects of satiety hormones (insulin and leptin) on the hypothalamus and the action of specific hypothalamic nuclei in regulating feeding and metabolic activity. Your answer should specify the specific area(s) in which the hormones bind (i.e. where there are receptors), the output(s) from the hormone binding area(s) to other hypothalamic areas, and the outputs from the hypothalamus to other brain/body areas that generate changes in food-seeking behavior and changes in metabolic rate throughout the body.

Explanation / Answer

Leptin is a hormone expressed by adipocytes. The amount of leptin secreted is controlled by another peptide hormone – Insulin. Leptin can cross the blood-brain barrier, and can diffuse into the hypothalamic nucleus. Hypothalamus expresses LRb (long leptin receptor). The following sequence of reactions follows this binding:

Leptin binds to LRb. This results in autophosphorylation of JAK2 (JAK is Janus kinase, a family of intracellular, non-receptor tyrosine kinases)

Activated JAK2leads to activation of STAT3 (signal transducer and activator of transcription)

STAT3 is translocated to nucleus to initiate transcription of neuropeptides

Neurons expressing the following neuropeptides are targets for leptin: NPY (neuron expressed neuropeptide Y), agouti-related peptide (AGRP), proopiomelanocortin (POMC). Paraventricular nucleus also is a target for leptin. This region of brain secretes the hormones TRH, CRH, and oxytocin. These hormones in turn, regulate pituitary gland, and are involved in energy metabolism

NPY stimulate food intake. It also function in reduction of energy expenditure and increase in weight

AGRP is an endogenous antagonist of MSH (MSH is derived from POMC)

Leptin binding to neurons regulate the neuropeptide expression by neurons. When leptin levels are low, energy expenditure is decreased and intake of food is increased

Low levels of leptin causes an increase in NPY/AGRP and decreased levels of MSH and CART (cocaine and amphetamine regulation)

High levels of leptin occurs when stomach is fully satiated. High leptin levelssuppress NPY?AGRP and increase the levels of alpha -MSH and CRH

The nuclei of hypothalamus express insulin signaling receptors. They are involved in energy metabolism. Insulin receptors are phosphorylated in the presence of insulin, increase binding of activated insulin receptor IRS-1 and 2 to PI3 kinase. This ultimately leads to upregulation of expression of POMC and CART, and down regulation of expression of NPY and AGRP

Related Questions

Navigate

• Browse (All)
• Browse P
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.