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Chapter 45: Adipose Tissue and Obesity: Associated Metabolic Disturbances

You are studying the responses of fat cells in culture to the addition of various pharmacologic compounds. You find that addition of a β-adrenergic agonist does not result in the expected change in mitochondrial proton gradients. This would indicate that there was most likely a defect in the function of which of the following?

A. adiponectin

B. adipose triglyceride lipase

C. fatty acid synthase

D. leptin

E. UCP1

Answer E: Norepinephrine binding to brown adipocytes triggers the activation of adenylate cyclase and the production of cAMP that in turn activates PKA. PKA phosphorylates and activates hormone-sensitive lipase, HSL. Activation of HSL leads to release of free fatty acids which are taken up by the mitochondria, similarly as they would be for purposes of oxidation; however, in BAT they interact with and activate the proton gradient uncoupling activity of uncoupling protein 1 (UCP1). Uncoupling the proton gradient releases the energy of that gradient as heat.

Experiments have been designed to assess the effects of a novel drug on the inflammatory responses of adipose tissue in laboratory mice. Addition of the drug to the diet of the mice demonstrates a clear reduction in the production and release of pro-inflammatory cytokines from adipose tissue. This experimental drug is most likely inhibiting the action of which of the following leading to the observed results?

A. adiponectin

B. leptin

C. monocyte chemotactic protein-1, MCP-1

D. vascular cell adhesion molecule-1, VCAM-1

E. vascular endothelial cell growth factor, VEGF

Answer C: The significance of inflammatory responses elicited via secretion of adipose tissue–derived (WAT) cytokines relates to the fact that their production and secretion is increased in obese individuals. One key change in adipose tissue that results in increased synthesis and release of pro-inflammatory adipokines is an increase in the percentage of macrophages resident within the tissue. Macrophages are a primary source of pro-inflammatory cytokines secreted by adipose tissue. The primary adipokine responsible for this infiltration is monocyte chemotactic protein-1 (MCP-1). Thus, inhibition of MCP-1 releases or function would limit increased monocyte infiltration and reduce the pro-inflammatory actions of adipose tissue.

The inflammatory activity of adipose tissue, particularly visceral fat, is enhanced in obese individuals. This effect of obesity is, in part, due to adipose tissue resistance to the actions of insulin. Insulin resistance in adipose tissue is reflected by a reduction ...

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