In fat cell

These agents activate PPAR-y a nuclear transcription factor important in fat cell differentiation and fatty acid metabolism. PPAR-yagonists enhance insulin sensitivity in muscle, liver, and fat tissues indirectly. Insulin must be present in significant quantities for these actions to occur. 

During fasting, the decrease in insulin and the increase in epinephrine activate hormone-sensitive lipase in fat cells, allowing fatty acids to be released into the circulation. 

The final step in signal transduction is the action of cAMP on the regulatory subunit of the enzyme, protein kinase A. This ubiquitous enzyme then phosphorylates and activates enzymes with functions specific to different cells and organs. In fat cells, protein kinase A activates lipase, which mobilizes fatty acids in muscle and liver cells, it regulates glycogenolysis and glycogen synthesis. 

The availability of a chemical to the cells is affected by where it is stored. First, lipophilic chemicals tend to get absorbed by and retained in fat cells, from which they are released slowly back into the bloodstream. Second, some chemicals are strongly bound to plasma proteins and are released to the cells more slowly over time. For example, acetaminophen (Tylenol ) does not bind strongly to plasma proteins, while diazepam (Valium ) does. Thus, diazepam will persist in the body for longer periods of time than will acetaminophen. Finally, some elements, such as fluorine, lead, and strontium, are bound up in bone for long periods of time. As bone slowly renews itself or is broken down under special circumstances such as pregnancy, the chemicals are released and can affect the mother and fetus. 

Acting as an intracellular second messenger, cAMP mediates such hormonal responses as the mobilization of stored energy (the breakdown of carbohydrates in liver or triglycerides in fat cells stimulated by B-adrenomimetic catecholamines), conservation of water by the kidney (mediated by vasopressin), Ca2+ homeostasis (regulated by parathyroid hormone), and increased rate and contractile force of heart muscle ( -adrenomimetic catecholamines). It also regulates the production of adrenal and sex steroids (in response to corticotropin or follicle-stimulating hormone), relaxation of smooth muscle, and many other endocrine and neural processes. 

Sympathomimetic drugs have important effects on intermediary metabolism. Activation of adrenoceptors in fat cells leads to... 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

Dopamine can thus be added to the list of hormones and neurotransmitters which can stimulate or inhibit cyclic AMP formation, depending upon their tissue of action. Thus, while dopamine stimulates cyclic AMP formation in parathyroid cells, superior cervical ganglia, retina and striatal tissue (27, 58-61), it inhibits the accumulation of the cyclic nucleotide in cells of the intermediate and anterior lobes of the pituitary gland. Opposite effects on the cyclic AMP system are also found with LHRH which stimulates and inhibits cyclic AMP levels in the anterior pituitary gland (62) and ovary (63), respectively. Similarly, alpha-adrenergic agents show opposite effects on cyclic AMP formation in brain (64) and platelets (65). PGE, stimulates cyclic AMP formation in the anterior pituitary gland (62) while it inhibits the same parameter in fat cells (66). 

In fat cells epinephrine stimulation of cyclic AMP accumulation and lipolysis is markedly reduced in hypothyroidism but enhanced in hyperthyroidism (see Ref. 79). Similar effects of altered thyroid status on the response to two other lipolytic hormones, ACTH and glucagon, have been reported suggesting that thyroid hormones regulate similarly either the different receptors of the various lipolytic hormones and/or a common step of the lipolytic pathway [80],... 

Growth factor receptors (These receptors fall into two main groups receptor tyrosine kinases and receptors that associate with cytoplasmic tyrosine Insulin1 Insulin Lower blood glucose promote glucose storage as glycogen in liver and skeletal muscle and as fat in fat cells... 

Triacylglycerol has no polar interaction with the membrane phospholipids and is either released into the cytosol as tiny lipid droplets or into the lumen of the ER. In fat cells, oil droplets in the cytosol coalesce, migrate toward and fuse with the large central oil droplets. In the liver and intestine, triacylglycerol is packaged into lipoproteins (VLDL and chylomicrons, respectively), which then are secreted into the circulation (see Fig. 13-11). 

Insulin also exerts a stimulatory effect on the synthesis of cholesterol in the liver. In this tissue, HMG-CoA reductase is activated. HMG-CoA reductase, like hormone-sensitive lipase, can exist in two forms one is phosphorylated (inactive) and the other is dephosphorylated (active). Phosphorylation of the enzyme depends on an increase in the cellular concentration of cAMP and activation of protein kinase. The dephosphorylation (activation) is catalyzed by a phosphatase. In fat cells, a similar phosphatase dephosphorylates (inactivates) hormone-sensitive lipase. Insulin stimulates the activity of the phosphatase in both liver and fat cells. In this way, active HMG-CoA reductase predominates in the liver cell and directs HMG-CoA into cholesterol synthesis, and in the fat cell hormone-sensitive lipase is inactivated. 

The four fat-soluble vitamins—A, D, E, and K—are found in fruits and vegetables, fish, liver, and dairy products. Although fat-soluble vitamins must be obtained from the diet, they do not have to be ingested every day. Excess vitamins are stored in fat cells, and then used when needed. Figure 29.5 shows the structure of these vitamins and summarizes their functions. 

Fatty acids are stored in this room (i.e., in fat cells) on glycerol coat racks (fig. 4.3) The three —OH groups of glycerol are the hooks of the 3-carbon coat rack. The fetty acids are the clothes that are placed on the coat racks. The products are called glycerides, namely ... 

Chylomicrons. Where would you go if you were a chylomicron For one thing, triglycerides, the main component of chylomicrons, are stored in fat cell.s, so chylo-... 

These reported actions of CLA could be mediated through a number of physiological mechanisms including increased fat oxidation (31) or inhibition of lipid accumulation in fat cells. Recent studies have started to investigate the physiological actions of individual isomers. It appears that the 10,12-tc isomer of CLA is mainly responsible for the effect of CLA on adiposity (32-34). 

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