Direct and indirect effects of leptin on preadipocyte proliferation and differentiation

Leptin has been shown to reduce body fat in vivo. Adipocytes express the leptin receptor; therefore, it is realistic to expect a direct effect of leptin on adipocyte growth and metabolism. In vitro studies examining the effect of leptin on adipocyte metabolism require supraphysiological doses of the protein to see a decrease in lipogenesis or stimulation of lipolysis, implying an indirect action of leptin. It also is possible that leptin reduces adipose mass by inhibiting preadipocyte proliferation (increase in cell number) and/or differentiation (lipid filling). Thus we determined direct and indirect effects of leptin on preadipocyte proliferation and differentiation in vitro. We tested the effect of leptin (0-500 ng/ml), serum from leptin-infused rats (0.25% by volume), and adipose tissue-conditioned medium from leptin-infused rats (0-30% by volume) on preadipocyte proliferation and differentiation in a primary culture of cells from male Sprague-Dawley rat adipose tissue. Leptin (50 ng/ml) stimulated proliferation of preadipocytes (P<0.05), but 250 and 500 ng leptin/ml inhibited proliferation of both preadipocyte and stromal vascular cell fractions (P<0.01), as measured by [3H]thymidine incorporation. Serum from leptin-infused rats inhibited proliferation of the adipose and stromal vascular fractions (P=0.01), but adipose tissue-conditioned medium had no effect on proliferation of either cell fraction. None of the treatments changed preadipocyte differentiation as measured by sn-glycerophosphate dehydrogenase activity. These results suggest that leptin could inhibit preadipocyte proliferation by modifying release of a factor from tissue other than adipose tissue.     

Mature adipocytes may be a source of stem cells for tissue engineering

Adipose tissue contains a large portion of stem cells. These cells appear morphologically like fibroblasts and are primarily derived from the stromal cell fraction. Mature (lipid-filled) adipocytes possess the ability to become proliferative cells and have been shown to produce progeny cells that possess the same morphological (fibroblast-like) appearance as the stem cells from the stromal fraction. A closer examination of mature adipocyte-derived progeny cells may prove to be an emerging area of growth/metabolic physiology that may modify present thinking about adipose tissue renewal capabilities. Knowledge of these cells may also prove beneficial in cell-based therapies for tissue repair, regeneration, or engineering.     

Obesity‐related hypertension: Pathogenesis,cardiovascular risk,and treatment—A position paper of the The Obesity Society and the American Society of Hypertension

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012)     

Nucleoside phosphatase and nucleotide tetrazolium reductase as markers of arteriolar differentiation in fetal pig tissue

Nucleoside phosphatase and nucleotide tetrazolium reductase reactions were studied as potential markers of arteriolar differentiation. Arteriolar systems were analyzed cytochemically and morphologically in a variety of fetal pig tissues at 70 and 110 days of gestation. In skeletal muscle and subcutaneous adipose tissue there were age dependent changes in phosphatase and reductase reactivity in arteriolar vessels. These changes were temporally associated with the morphological differentiation of the tunica medial arteriolar layer. There were no age dependent changes in the cytochemistry of arterioles in liver and cardiac muscle. In the youngest fetuses, arterioles in liver and cardiac muscle displayed a typical tunica medial layer (normal morphology). The cytochemical reactions (phosphatase, reductase) of arterioles in cardiac muscle and liver from 70 (and 110) days old fetuses were identical to cytochemical reactions of arterioles in muscle and adipose tissue from 110 days old fetuses. In the skin, there were age dependent increases in phosphatase reactive arterioles and capillaries. Capillary staining (phosphatase) and capillary bed size were inversely correlated in the skin. Capillaries in skeletal muscle, cardiac muscle, adipose tissue and liver were not phosphatase reactive. These results indicate that the morphological and cytochemical differentiation of arterioles is dependent on tissue and age in the fetal pig. Furthermore, several histochemical techniques (phosphatase, reductases) are validated as simple means to analyze arteriolar differentiation in general.     

Histochemistry of connective tissue cells in subcutaneous adipose tissue of normal and decapitated pig fetuses

Connective tissue cells that are histochemically and morphologically distinct from 'fibroblasts' are localized around developing hair follicles in the pig and rat. Immature adipose tissue is limited to small areas immediately around fully descended hair follicles in the rat hypodermis. In the present study, connective tissue around large nerves and blood vessels in fetal pig subcutaneous tissue was examined for the presence of enzymes typical of adipocytes. Samples from decapitated pig fetuses were studied so that the effects of an altered hormonal profile could be examined. Samples of dorsal subcutaneous adipose tissue were obtained from fetuses at 65, 70, 85, 90, 110, and 112 days of gestation. Fetuses were decapitated in utero at 45 days of gestation, and adipose tissue samples were obtained from these fetuses at 110 days of gestation. A close spatial relationship was observed between the growth of large blood vessels and nerves and fat cell cluster development in the older (greater than 70 days) fetuses. Connective tissue cells that were contiguous with fat cell clusters were histochemically identical to adipocytes. The lipid histochemistry of the reactive connective tissue cells (histochemically identical to adipocytes) was variable in young fetuses. In all 110-and 112-day-old fetuses, the reactive cells contained lipid, whereas the reactive cells in decapitated fetuses were devoid of lipid. The reactive connective tissue cells were not associated with capillaries and did not contain basement membranes. The histochemistry of these cells suggests that they respond to a particular hormonal or metabolic profile as do adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acute sprint interval cycling and energy replacement on postprandial lipemia

High postprandial blood triglyceride (TG) levels increase cardiovascular disease risk. Exercise interventions may be effective in reducing postprandial blood TG. The purpose of this study was to determine the effects of sprint interval cycling (SIC), with and without replacement of the energy deficit, on postprandial lipemia. In a repeated-measures crossover design, six men and six women participated in three trials, each taking place over 2 days. On the evening of the first day of each trial, the participants either did SIC without replacing the energy deficit (Ex-Def), did SIC and replaced the energy deficit (Ex-Bal), or did not exercise (control). SIC was performed on a cycle ergometer and involved four 30-s all-out sprints with 4-min active recovery. In the morning of day 2, responses to a high-fat meal were measured. Venous blood samples were collected in the fasted state and at 0, 30, 60, 120, and 180 min postprandial. There was a trend toward a reduction with treatment in fasting TG (P = 0.068), but no significant treatment effect for fasting insulin, glucose, nonesterified fatty acids, or betahydroxybutryrate (P > 0.05). The postprandial area under the curve (mmol·l(-1)·3 h(-1)) TG response was significantly lower in Ex-Def (21%, P = 0.006) and Ex-Bal (10%, P = 0.044) than in control, and significantly lower in Ex-Def (12%, P = 0.032) than in Ex-Bal. There was no treatment effect (P > 0.05) observed for area under the curve responses of insulin, glucose, nonesterified fatty acids, or betahydroxybutryrate. SIC reduces postprandial lipemia, but the energy deficit alone does not fully explain the decrease observed.     

Genistein inhibits differentiation of primary human adipocytes

Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.