White adipose tissue (WAT) consists of various cell types, including adipocytes which store triglycerides (TG). These adipocytes develop from preadipocytes during human gestation and can continue to differentiate throughout life. Adipocyte differentiation is facilitated by several transcription factors, one of which is SREBP1C. SREBP1C is activated by lipids, insulin, growth factors, and cytokines. Another important transcription factor in WAT is PPARγ, which promotes the expression of genes involved in TG storage. As a result, an increase in food consumption leads to the activation of SREBP1C and PPARγ, causing preadipocytes to differentiate into small adipocytes and upregulating enzymes that allow for the storage of excess fat.

Adipose tissue produces various paracrine and endocrine factors, including adiponectin, TNF-α, resistin, interleukin-6, angiotensinogen, and acylation-stimulating protein.

Leptin is a protein derived from adipocytes that signals information to the hypothalamus about adiposity and nutrition. This information controls eating behavior and energy expenditure. Leptin deficiency in mice and humans leads to severe obesity. Initially, there was hope that leptin therapy could combat morbid obesity. However, administering leptin to individuals with diet-induced obesity does not have a significant effect on appetite or energy expenditure. Obese individuals already have elevated levels of endogenous leptin and appear to have developed resistance to its effects.

Leptin plays an important role in regulating lipid storage in peripheral tissues. It directs excess caloric intake into adipose tissue, protecting peripheral tissues (e.g., liver, skeletal muscle, cardiac muscle, beta cells) from excessive lipid accumulation. Despite opposing the lipogenic actions of insulin, this action of leptin significantly contributes to maintaining insulin sensitivity in peripheral tissues. Leptin also acts as a signal that the body has sufficient energy stores for reproduction and enhances erythropoiesis, lymphopoiesis, and myelopoiesis. For example, women with anorexia nervosa have extremely low levels of leptin, resulting in low ovarian steroids, amenorrhea, anemia, and immune dysfunction.

Structure, Synthesis, and Secretion
Leptin is a 16-kDa protein secreted by mature adipocytes and structurally related to cytokines. It was discovered that SREBP2 is a transcription factor located in the endoplasmic reticulum (ER). In the presence of high intracellular cholesterol, SREBP2 is held in the ER by a lipid-sensing protein called SCAP (SREBP cleavage–activating protein). When cellular sterol levels are depleted, SCAP escorts SREBP2 to the Golgi, where it is sequentially cleaved by proteases and released into the cytoplasm. SREBP2 then translocates to the nucleus and increases the transcription of genes involved in cholesterol synthesis and uptake. Another member of this transcription factor family, SREBP1C, is highly expressed in adipose and liver tissues. In contrast to SREBP2, SREBP1C stimulates genes involved in fatty acid and triglyceride synthesis. The regulation of SREBP1C occurs at the transcriptional level of the SREBP1C gene, with cleavage induced by polyunsaturated fatty acids and activation by the MAPK pathway.
White adipose tissue (WAT) is composed of several cell types. The TG-storing cell is called the adipocyte. These cells develop from preadipocytes during gestation in humans. This process of adipocyte differentiation, which may continue throughout life, is promoted by several transcription factors. One of these factors is SREBP1C, which is activated by lipids as well as insulin and several growth factors and cytokines. Another important transcription factor in WAT is PPARγ. Activated PPARγ promotes expression of genes involved in TG storage. Thus an increase in food consumption leads to activation of SREBP1C and PPARγ, which increase the differentiation of preadipocytes into small adipocytes and upregulation of enzymes within these cells to allow storage of excess fat.
Adipose tissue produces paracrine and endocrine factors, including adiponectin, TNF-α, resistin, interleukin-6, angiotensinogen, and acylation-stimulating protein.
Leptin is an adipocyte-derived protein that signals information to the hypothalamus about the degree of adiposity and nutrition, which in turn controls eating behavior and energy expenditure. Leptin-deficient mice and humans become morbidly obese. These findings originally raised hope that leptin therapy could be used to combat morbid obesity. However, administration of leptin to individuals who suffer from diet-induced obesity does not have a significant anorectic or energy-consuming effect. In fact, obese individuals already have elevated endogenous circulating levels of leptin and appear to have developed leptin resistance.
Leptin has an important role in liporegulation in peripheral tissues. Leptin protects peripheral tissues (e.g., liver, skeletal muscle, cardiac muscle, beta cells) from accumulation of too much lipid by directing storage of excess caloric intake into adipose tissue. This action of leptin, though opposing the lipogenic actions of insulin, contributes significantly to maintenance of insulin sensitivity (as defined by insulin-dependent glucose uptake) in peripheral tissues. Leptin also acts as a signal that the body has sufficient energy stores to allow reproduction and to enhance erythropoiesis, lymphopoiesis, and myelopoiesis. For example, in women suffering from anorexia nervosa, leptin levels are extremely low and result in low ovarian steroids, amenorrhea (lack of menstrual bleeding), anemia from low red blood cell production, and immune dysfunction.
Structure, Synthesis, and Secretion
Leptin, a 16-kDa protein secreted by mature adipocytes, is structurally related to cytokines. Thus it is sometimes
SREBP2 wasdiscoveredasatranscriptionfactorthatresidesinthemembraneoftheendoplasmicreticulum(ER).Inthepresenceofhighintracellularcholesterol,SREBP2isheldintheERbyalipid-sensingproteincalledSCAP (SREBPcleavage–activatingprotein).Inresponsetodepletedsterols,SCAPescortsSREBP2totheGolgi,whereSREBPiscleavedsequentiallybyproteasesandreleasedintothecytoplasm.SREBP2thentranslocatestothenucleusandincreasesthetranscriptionofgenesinvolvedinsynthesisanduptakeofcholesterol.AmorerecentlydiscoveredmemberofthistranscriptionfactorfamilyisSREBP1C, whichishighlyexpressedinadiposeandliver.IncontrasttoSREBP2,SREBP1CstimulatesgenesinvolvedinsynthesisofFAandTG.RegulationofSREBP1CoccursatthetranscriptionalleveloftheSREBP1C gene,withcleavageinducedbypolyunsaturatedfattyacidsandactivationbytheMAPKpathway.