SEARCH · PubMed Health

Results for “Adiposity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2004

Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats.

There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a low-protein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed > or =1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity.

Adipose Tissue↗

PubMed2002

Exclusive action of transmembrane TNF alpha in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance.

Aberrant TNF alpha expression in adipocytes is a molecular mechanism by which insulin action is modulated in adipose tissue. While this might be a compensatory response to limit adipose expansion, neither the mechanisms underlying this local effect nor its systemic biological consequences have been studied. It is also not clear whether TNF alpha-induced insulin resistance in adipocyte alone is responsible for systemic insulin resistance in the absence of obesity. In a transgenic mouse model deficient in endogenous TNF alpha, we demonstrate that specific expression of the transmembrane TNF alpha (mTNF alpha) in adipocytes leads to decreased whole body adipose mass, and local, but not systemic insulin resistance. These data demonstrate that exclusive action of TNF alpha in adipose tissue strongly inhibits insulin action at this site and leads to reduced adiposity in mice. However, this isolated adipocyte insulin resistance in the context of reduced fat mass and/or the absence of obesity is insufficient to alter systemic glucose homeostasis.

Adipocytes↗

PubMed2000

Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture.

Leptin is mainly produced in white adipose tissue and acts both at distant sites and locally at the tissue from which it originates. The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. Both leptin and its receptor were present in mature unilocular fat cells. The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. Other cellular components of human white adipose tissue were characterized by anti-CD31 for endothelial cells, anti-CD68 for macrophages, and antibodies specifically labeling B-cells and T-cells. In addition to fat cells, endothelial cells were immunopositive for the full-length leptin receptor. On the ultrastructural level, leptin was mainly found attached to cellular membranes and in small alveolate vesicle-like structures in the cytoplasm of adipocytes. Leptin was also present on the cell membranes of endothelial cells and macrophages. We conclude that the expression of the Ob-R in human white adipose tissue is not restricted to adipocytes but is present in resident endothelial and immune cells. Ultrastructural localization studies revealed an association of leptin with cell membranes and small vesicles. The cellular and subcellular distribution of leptin and its receptor suggests an important autocrine and paracrine role for leptin in human adipose tissue.

Adipose Tissue↗

PubMed1989

Glycerolipid biosynthesis in porcine adipose tissue in vitro: effect of adiposity and depot site.

To compare genetic differences in glycerolipid biosynthesis, rates were determined in s.c. adipose tissue of lean and obese pigs at 28, 60 and 110 d of age. To compare depot-specific differences, glycerolipid biosynthetic rates were determined in outer s.c., middle s.c., perirenal and omental adipose tissues obtained from 105-kg contemporary pigs. Rates were determined with a 700 x g infranatant fraction of an adipose tissue homogenate by measuring glycerophosphate incorporation into total lipids (mostly phosphatidic acid) during 4 min. This assay represents entrance of substrates into the glycerolipid synthesis pathway or glycerophosphate acyltransferase (GPAT) activity. Rates measured for 60 min represent maximal synthesis of glycerolipid (more triacylglycerol than phosphatidic acid) or lipid synthesis capacity (LSC). Adipocyte diameter and volume were greater for adipose tissue of obese than of lean pigs both at 60 and 110 d. When expressed per cell, activity of GPAT and LSC were similar for lean and obese pigs at 28 d. At 60 d and 110 d, LSC was greater for obese than for lean pigs; GPAT activity was greater at 60 but not at 110 d in obese than in lean pigs. Expressed on a cell basis, GPAT activity was highest in omental and outer s.c., intermediate in perirenal and lowest in middle s.c. adipose tissue depots. Lipid synthesis capacity was highest in perirenal and lowest in outer and middle s.c. depots. Our results indicate that the LSC assay was more closely related to the accretion of fat in vivo than to GPAT activity.

Adipose Tissue↗

PubMed2002

Effect of nitric oxide donors on isoprenaline-induced lipolysis in rat epididymal adipose tissue: studies in isolated adipose tissues and immobilized perfused adipocytes.

The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60% of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis.

Adipose Tissue↗

PubMed2006

Adipose tissues differentiated by adipose-derived stem cells harvested from transgenic mice.

OBJECTIVE: To induce adipocyte differentiation in vitro by adipose-derived stromal cells (ASCs) harvested from transgenic mice with green fluorescent protein (GFP)and assess the possibility of constructing adipose tissues via attachment of ASCs to type I collagen scaffolds. METHODS: Inguinal fat pads from GFP transgenic mice were digested by enzymes for isolation of ASCs (primary culture). After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks, and the adipocyte differentiation by ASCs in vitro was assessed by morphological observation and Oil Red O staining. Then they were attached to collagen scaffolds and co-cultured for 12 hours, followed by hypodermic implantation to the dorsal skin of nude mice for 2 months. The newly-formed tissues were detected by HE staining. RESULTS: The cultured primary stem cells were fibroblast-like and showed active proliferation. After being incubated in an adipocyte differentiation medium, the lipid droplets in the cytoplasm accumulated gradually and finally developed into mature adipocytes, which showed positive in Oil Red O staining. A 0.5-cm3 new tissue clot was found under the dorsal skin of the nude mice and it was confirmed as mature adipose tissues by fluorescent observation and HE staining. CONCLUSIONS: ASCs can successfully differentiate adipose tissues into mature adipocytes, which exhibit an adipocyte-like morphology and express as intracytoplasmic lipid droplets. It is an efficient model of adipose tissues engineered with ASCs and type I collagen scaffolds.

Adipogenesis↗

PubMed1978

[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism].

The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue.

Adipose Tissue↗

PubMed1996

Adiposity and body mass indices in children: Benn's index and other weight for height indices as measures of relative adiposity.

OBJECTIVES: Several forms of weight for height or body mass index (BMI) are in widespread epidemiological and clinical use as measures of relative adiposity. The form derived by Benn for adults has been advocated for use in children and practical aspects of this proposition are considered. METHODS: Height and weight data from 8492 Australian schoolchildren aged 7 to 15 were studied. A subsample of 2753 children aged 9, 12 and 15 years had skinfold thicknesses measured. The sum of four skinfolds and percentage body fat predicted from skinfolds were used as measures of adiposity. RESULTS: Of the various forms of power type BMI examined, weight/(height)2 was most closely associated with adiposity in this sample. Benn's assumption of low correlation between height and adiposity (which holds in adults) was not satisfied in children. CONCLUSIONS: Benn's index is not recommended for general use as a body mass index in children. However, Benn's relative weight has advantages as an indirect measure of adiposity which may be of value in epidemiological studies among children.

Adipose Tissue↗

PubMed1973

Studies on the compartmentation of lipid in adipose cells. II. Cholesterol accumulation and distribution in adipose tissue components.

Adipose tissue was shown to contain 0.6-1.6 mg of cholesterol per gram wet weight. When expressed per unit of protein or organ mass, fat tissue contains more cholesterol than most other organs or membranes. The cholesterol content of fat tissue increased with the age and weight of the rat. Over 95% of adipose tissue sterols was cholesterol, and most of it was free. In young (150-165 g) rats two-thirds of fat tissue cholesterol was in collagenase-derived adipocytes while in older rats (450-480 g) 90% of fat tissue cholesterol was in adipocytes and the remainder was in stromal-vascular elements. Age-related differences in subcellular cholesterol distribution were also observed. The cholesterol/phospholipid molar ratios of purified plasma membrane fractions from small and large fat cells were identical (0.22-0.25), thus resembling muscle and liver membranes. 7.5 days after intravenous administration of [4-(14)C]cholesterol the specific activity of adipose cholesterol exceeded that of plasma cholesterol. At 28 days the specific activity of adipose and muscle cholesterol exceeded that of plasma three- to fivefold. The t((1/2)) disappearance of adipose tissue cholesterol was approximately 27 days, which is consistent with its function as a slowly turning over storage pool. Thus, fat tissue is a major cholesterol storage organ. This may well account for the marked expansion of the slowly exchangeable cholesterol pool (pool B) observed in obesity.

Adipocytes↗

PubMed2003

PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion.

This study sought to determine whether the adipose depot-specific (subcutaneous [SF] vs. visceral [VF]) action of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists on fat deposition extends to the expression of lipoprotein lipase (LPL) and other key adipose lipid metabolism genes, and whether changes in LPL impact triglyceridemia. Rats were fed a standard diet or an obesity-promoting diet for 3 weeks, with or without treatment with COOH, a nonthiazolidinedione PPAR-gamma agonist. Treatment effects were essentially similar in both dietary cohorts. COOH did not affect weight gain, but increased SF (inguinal) fat mass twofold and reduced VF (retroperitoneal) accretion by half. Corresponding depot-specific alterations were observed in mRNA levels of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD-1) and the thermogenic modulator uncoupling protein 1 (UCP-1). COOH increased brown adipose tissue (BAT) weight and LPL availability by five- to eightfold. In rats refed standard diet after a 24-h fast, COOH reduced the insulin excursion by half. The agonist increased SF LPL activity and mRNA levels, but had no effect on VF LPL. The two- to threefold postprandial increase in plasma triglycerides (TGs) was abrogated in COOH-treated rats, likely in part because of increased LPL in SF and BAT. Thus PPAR-gamma agonist treatment had a powerful, site-specific effect on adipose metabolism and lipid deposition, and greatly impacted the postprandial handling of TG-rich lipoproteins. These depot-specific effects may be mediated by differential regulation of key metabolic genes, including LPL, 11beta-HSD-1, and UCP-1.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

Adrenalectomy reduces adiposity by decreasing food efficiency, not direct effects on white adipose tissue.

OBJECTIVE: This study was conducted to establish the effects of adrenalectomy (ADX) on adipose tissue metabolism in male Sprague-Dawley rats fed a standard chow diet. RESEARCH METHODS AND PROCEDURES: The effects of adrenalectomy on adipose cell size, lipoprotein lipase activity, and basal and insulin-stimulated glucose conversion to lipid and lipolysis were measured. RESULTS: ADX decreased body weight gain during the post-operative period in the absence of changes in food intake; feed efficiency was decreased significantly. ADX decreased adipocyte size by 30%. ADX increased adipocyte response to the effect of submaximal concentrations of insulin on lipid synthesis and lipolysis. ADX decreased maximally insulin-stimulated lipid synthesis, but this effect was accounted for by decreased adipocyte size. In contrast, ADX had no effect on maximally insulin-inhibited lipolysis. ADX did not affect heparin-releasable LPL. The small effect of ADX on residual extractable adipose tissue LPL activity was accounted for by decreased fat cell size. DISCUSSION: ADX decreased adiposity in the absence of changes in food intake, lipoprotein lipase activity, and adipocyte lipid metabolism. The effect is best attributed to decreased feed efficiency.

Adipocytes↗

PubMed2003

Identification of cathepsin K as a novel marker of adiposity in white adipose tissue.

In obesity, adipocytes undergo dramatic morphological and molecular changes associated with alterations in their gene expression profile. To identify genes differentially modulated in white adipose tissue (WAT) of obese db/db mice compared to wild type (wt) mice, we utilized RNA fingerprinting. Among the 52 candidates that we identified, we focused here on cathepsin K (ctsk), a cysteine protease, prevalently localized in lysosomes and involved in bone extracellular matrix degradation. In db/db mice, WAT ctsk mRNA was elevated 5.9-fold, as were Mitf and TFE3 (2- and 3.3-fold respectively), two transcription factors involved in ctsk induction in osteoclasts. Moreover, the level of WAT ctsk mRNA was increased in other obese models including A(y), fat, and tubby (2.8-, 3.2-, and 4.9-fold respectively) and decreased in mice undergoing weight loss. Despite the ubiquitous distribution of the ctsk transcript, we demonstrated that the obesity related increase is specific to the adipocytes. Further, in vitro experiments proved that the abundance of ctsk transcript increases upon adipose conversion of the established cell line of preadipocytes 3T3-F442A. In addition, ctsk gene expression was examined in adipose tissue of 21 lean and obese male subjects and significant correlations with BMI (r = 0.54, P = 0.012) and plasma leptin levels (r = 0.54, P = 0.015) were found. In conclusion, the WAT of obese db/db mice exhibits a different expression profile from that of the wt mice, and cathepsin K can be considered a novel marker of obesity and a target for the inhibition of adipose mass growth.

Adipocytes↗

PubMed2002

Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue.

Interleukin-15 (IL-15) is a proinflammatory cytokine with multifunctional effects outside the immune system. Previous studies have indicated that treatment of normal rats with IL-15 reduces white adipose tissue (WAT) mass, but it was unclear if these effects were direct or indirect. In the present study, the effects of IL-15 on WAT mass and lipid metabolism were studied in two genetic models of obesity: the leptin receptor-negative fa/fa Zucker rat and the leptin-deficient ob/ob mouse. Lean Zucker rats, lean (+/+), and obese mice (ob/ob) responded to IL-15 with reductions in WAT mass and lipoprotein lipase activity (LPL), with no decreases in food intake. In contrast, fa/fa Zucker rats did not respond to IL-15 administration by any of the above measures of fat mass or lipid metabolism. In addition, ribonuclease protection assays (RPAs) were used to demonstrate that all three subunits (gamma(c), beta and alpha) of the IL-15 receptor complex are expressed by rat and mouse WAT, suggesting that the effects of IL-15 on adipose tissue metabolism could be direct. Additionally, the fa/fa rats expressed 84% lower levels of the gamma(c) signaling receptor subunit than lean Zucker rats, suggesting this decrease may play a role in the lack of adipose tissue response to IL-15 in the fa/fa genotype and lending further support for a direct action of IL-15 on adipose tissue.

Adipose Tissue↗

PubMed1979

The early development of white adipose tissue. Effects of litter size on the lipoprotein lipase activity of four adipose-tissue depots, serum immunoreactive insulin and tissue cellularity during the first four weeks of life in the rat.

1. Newborn rats were reared in litters of either four or sixteen individuals. The animals from the small litters gained body weight more rapidly than those from large litters during the first 29 days of postnatal life studied. 2. The relative weights of the perigenital, perirenal, subcutaneous and intramuscular white-adipose-tissue sites in the animals from small litters indicated their relative obesity compared with controls. 3. The adipose depots from animals reared in small litters had a greater proportion of lipid present, by weight, and had a greater number of larger fat-cells present in them compared with the depots of animals reared in large litters. 4. Compared with both normal-sized litter controls and animals reared in sixteens, during the period of study the animals from small litters were hypertriacylglycerolaemic but normocholesterolaemic. 5. During suckling the blood glucose concentrations of animals reared in fours were increased, as were the concentrations of circulating immunoreactive insulin. 6. During the 29 days of life studied, in general, the lipoprotein lipase activity of adipose depots from animals reared in fours was greater than for animals in large litters when expressed as mumol of nonesterified fatty acid released from the substrate/h per g fresh weight of tissue, per depot, or per million fat-cells, but were similar per cm(2) of fat-cell surface area. 7. The previously noted [Cryer & Jones (1978) Biochem. J.172, 319-325] pattern of mid-suckling elevation, late-suckling decline and post-weaning increase in the lipoprotein lipase activity of the four white-adipose depots studied was not obliterated by the nutritional manipulations employed. 8. The relation of the enzyme-activity changes and their hormonal stimuli to triacylglycerol accumulation in fat-cells of animals from large and small litters is discussed in relation to the possible significance they may have to our understanding of neonatally induced obesity.

Adipose Tissue↗

PubMed1980

The development of white adipose tissue. Effect of litter size on the lipoprotein lipase activity of four adipose-tissue depots, serum immunoreactive insulin and tissue cellularity during the first year of life in male and female rats.

(1.) Male and female rats reared in litters of four gained body weight more rapidly than animals reared in litters of 16. The differences were more marked in males than females and became less marked in both sexes with advancing age. (2.) The relative weights of the perigenital, perirenal, subcutaneous and intramuscular white-adipose-tissue sites in the animals from small litters indicated their relative obesity compared with animals from large litters. A sex-related difference in the distribution of adipose tissue between the four sites was seen in animals reared in litters of both four and 16. (3.) Although at 30 days of age all the animals had more numerous and larger fat-cells in their white-adipose-tissue depots than animals reared in large litters, the pattern of change thereafter was both site- and sex-specific. During the post-weaning period (30-300 days), although detailed differences were apparent between sites, a general pattern of increased cell size in males and increased cell numbers in females emerged as being the important determinants responsible for the differences in depot sizes seen when animals from litters of four and 16 were compared. (4.) Lipoprotein lipase activities, expressed as units/g fresh wt. of tissue, in the depots of animals reared in groups of four were unaltered compared with those reared in groups of sixteen during the post-weaning period (47-300 days of age), and enzyme activities expressed per depot merely reflected differences in tissue weights. (5.) Lipoprotein lipase activities per 10(6) cells were higher in males reared in fours compared with those reared in sixteens of equivalent age, but were unaltered for females. (6.) The persistent hyperinsulinaemia of animals reared in litters of four is discussed in relation to the observed differences in enzyme activity and white-adipose-tissue cellularity.

Adipose Tissue↗

PubMed1998

Induction of aromatase activity in human adipose tissue stromal cells by extracellular nucleotides--evidence for P2-purinoceptors in adipose tissue.

Here we describe properties of the P2-purinoceptor, which is involved in the regulation of the key enzyme of estrogen biosynthesis, aromatase cytochrome P-450, in stromal cells from human adipose tissue. Aromatase activity induced by cortisol and platelet-derived growth factor BB (PDGF-BB) is further increased by addition of ATP, ADP, AMP and, albeit with reduced potency, adenosine, GTP and adenosine(5')tetraphospho(5') adenosine. Stable P1-purinoceptor agonists are inactive, whereas P2X-purinoceptor agonists mimic the effects of purine(s) (nucleotides). Prior incubation of cells with a P2-purinoceptor antagonist, but not P1-purinoceptor antagonists, blocks augmentation of aromatase activity by all ligands. Nucleotides, but not adenosine, retain their ability to augment aromatase activity in the presence of adenosine deaminase, indicating that they do not act via their metabolite adenosine. These results lead to the conclusion, that at least one member of the P2-subclass of purinoceptors exists in adipose tissue and is involved in modulation of aromatase activity in vitro. The pharmacological profile of the P2-site differs from those reported for cloned P2-purinoceptors, but is similar to that of the P2X-subclass. Therefore, a combined response of different members of the P2X-purinoceptor subclass or of members of different P2-purinoceptor subclasses cannot be discounted. Purinoceptor activation triggers cytoplasmic calcium transients, which, in contrast to aromatase induction, are independent from the presence of cortisol and PDGF-BB. Therefore the involved P2-purinoceptor(s) seem(s) to be constitutively expressed in human adipose tissue stromal cells. P2-purinoceptor(s) might provide a direct link between sympathetic nerve activity and estrogen biosynthesis in human adipose tissue. Furthermore it (or they) may contribute to the regulation of lipolysis.

Adenosine↗

PubMed1995

Aromatase P450 gene expression in human adipose tissue. Role of a Jak/STAT pathway in regulation of the adipose-specific promoter.

In the present report we describe a heretofore unrecognized role for a Jak/STAT signaling pathway, namely the stimulation of expression of the aromatase P450 (CYP19) gene, and hence of estrogen biosynthesis, in human adipose tissue. Expression of this gene in adipose tissue as well as in adipose stromal cells maintained in the presence of serum and glucocorticoids is regulated by a distal TATA-less promoter, I.4, which contains a glucocorticoid response element, an Sp1 binding site, and an interferon-gamma activation site (GAS) element. The stimulatory action of serum (in the presence of dexamethasone) can be replaced by interleukin (IL)-11, leukemia inhibitory factor, and oncostatin-M, as well as by IL-6, providing the IL-6 soluble receptor is also present. Stimulation of the cells by these factors led to rapid phosphorylation of Jak1, but not Jak2 or Jak3, on tyrosine residues. STAT3 but not STAT1 was also phosphorylated and bound to the GAS element in the I.4 promoter region. When regions of this promoter were fused upstream of the chloramphenicol acetyltransferase reporter gene and transfected into the cells, mutagenesis or deletion of the GAS element led to complete loss of reporter gene expression. Since adipose tissue is the major site of estrogen biosynthesis in men and in postmenopausal women, this pathway involving a Jak/STAT signaling mechanism acting together with glucocorticoids and Sp1 appears to be the principal means whereby estrogen biosynthesis is regulated in the elderly.

Adipose Tissue↗

PubMed2005

The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity.

Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, much less is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome proliferator-activated receptor gamma angiopoietin-related protein) was previously identified as a target of hypolipidemic fibrate drugs and insulin-sensitizing thiazolidinediones. Using transgenic mice that mildly overexpress FIAF in peripheral tissues we show that FIAF is an extremely powerful regulator of lipid metabolism and adiposity. FIAF overexpression caused a 50% reduction in adipose tissue weight, partly by stimulating fatty acid oxidation and uncoupling in fat. In addition, FIAF overexpression increased plasma levels of triglycerides, free fatty acids, glycerol, total cholesterol, and high density lipoprotein (HDL)-cholesterol. Functional tests indicated that FIAF overexpression severely impaired plasma triglyceride clearance but had no effect on very low density lipoprotein production. The effects of FIAF overexpression were amplified by a high fat diet, resulting in markedly elevated plasma and liver triglycerides, plasma free fatty acids, and plasma glycerol levels, and impaired glucose tolerance in FIAF transgenic mice fed a high fat diet. Remarkably, in mice the full-length form of FIAF was physically associated with HDL, whereas truncated FIAF was associated with low density lipoprotein. In human both full-length and truncated FIAF were associated with HDL. The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization. Our data indicate that disturbances in FIAF signaling might be involved in dyslipidemia.

Adipose Tissue↗