Metabolism of adipose tissue in intraabdominal depots of nonobese men and women

Adipocyte size, lipoprotein lipase (LPL) activity, and the lipolytic response to noradrenaline and isoproterenol were studied in three intraabdominal depots (mesenteric, omental, retroperitoneal), as well as in subcutaneous abdominal adipose tissue, in nonobese groups of middle-aged men and in premenopausal and postmenopausal women. Subcutaneous adipocytes were larger than intraabdominal adipocytes in all groups. The men had large adipocytes in all intraabdominal depots as compared with the women. The premenopausal women seemed to have low LPL activity in intraabdominal depots. Two types of responses to catecholamine-stimulated lipolysis were observed: a similar response from mesenteric and omental (portal) fat depots and from retroperitoneal and subcutaneous abdominal (nonportal) fat depots. Young women had higher lipolysis in nonportal than in portal adipose tissues. In the men the reverse characteristics were found. These dissimilarities seem to be based on differences in beta-adrenergic responsiveness. Postmenopausal women showed no differences between depots. The differences in lipolytic responsiveness between these groups might be caused by sex steroid hormones.     

Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2

Regional variation of adipose tissue triglyceride breakdown (lipolysis) has been suggested to play a role for the health consequences of some forms of obesity. Thus, in the present study we investigated the regulation of lipolysis in isolated adipocytes obtained from different fat depots in females. Intra-abdominal adipose tissue (omental) and subcutaneous abdominal adipose tissue were obtained from the same individuals undergoing abdominal surgery (n = 9); in addition, adipocytes from the subcutaneous gluteal region (n = 12) and from mammary adipose tissue (n = 5) were investigated. The lipolytic/antilipolytic properties of epinephrine (EPI), insulin, clonidine, and prostaglandin E2 (PGE2) were investigated. The most prominent observation was that EPI had none or only minor lipolytic effect in adipocytes from the subcutaneous regions, but significantly enhanced lipolysis by approximately 500% in omental adipocytes (P less than .001). In the presence of the alpha 2-adrenergic antagonist, yohimbine, EPI had similar stimulatory effects (fourfold to fivefold) in all fat depots. The antilipolytic compounds, insulin and clonidine, had greatly reduced antilipolytic properties in omental adipocytes as compared with subcutaneous adipocytes (P less than .01 and P less than .05, respectively). On the other hand, PGE2 had similar antilipolytic properties in adipocytes from the various depots. In conclusion, we found great regional variation in the regulation of lipolysis. Particularly, EPI was much more lipolytic in omental adipocytes than in subcutaneous adipocytes, mainly due to an enhanced functional alpha 2-receptor activity in subcutaneous adipocytes. These in vitro data suggest that free fatty acids (FFA) are more readily mobilized from omental adipose tissue than from subcutaneous adipose tissue.     

Regional differences in adipose tissue metabolism in obese men

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P<.005). Basal lipolysis and lipolytic responses to isoproterenol, forskolin, or dibutyryl cyclic adenosine monophosphate, expressed either as a function of cell number or as a fold response over basal levels, were not significantly different in omental vs subcutaneous fat cells. When stratifying the sample in tertiles of waist circumference, adipocyte diameter was similar in the omental and subcutaneous depots for all adiposity values. Omental adipocyte size reached a plateau in the 2 upper tertiles of waist circumference, that is, from a waist circumference of 125 cm and above. Lipoprotein lipase activity was significantly higher in omental cells in the middle tertile of waist circumference (P=.05), and no regional difference was noted in lipolysis values across waist circumference tertiles. In conclusion, in normal-weight to morbidly obese men, although adipocyte size and lipolysis tended to increase with higher waist circumference, no difference was observed between the omental and subcutaneous fat depot.     

Regional differences in the control of lipolysis in human adipose tissue

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.     

Regional variation in adipose tissue insulin action and GLUT4 glucose transporter expression in severely obese premenopausal women

Summary Insulin action and GLUT4 expression were examined in adipose tissue of severely obese premenopausal women undergoing gastrointestinal surgery. Fat samples were taken from three different anatomical regions: the subcutaneous abdominal site, the round ligament (deep abdominal properitoneal fat), and the greater omentum (deep abdominal intraperitoneal fat). The stimulatory effect of insulin on glucose transport and the ability of the hormone to inhibit lipolysis were determined in adipocytes isolated from these three adipose depots. Insulin stimulated glucose transport 2–3 times over basal rates in all adipocytes. However, round ligament adipose cells showed a significantly greater responsiveness to insulin when compared to subcutaneous and omental adipocytes. Round ligament fat cells also displayed the greatest sensitivity and maximal antilipolytic response to insulin. We also investigated whether regional differences in fat cell insulin-stimulated glucose transport were linked to a differential expression of the GLUT4 glucose transporter. GLUT4 protein content in total membranes was 5 and 2.2 times greater in round ligament adipose tissue than in subcutaneous and omental fat depots, respectively. Moreover, GLUT4 mRNA levels were 2.1 and 3 times higher in round ligament than in subcutaneous or omental adipose tissues, respectively. Adipose tissue GLUT4 protein content was strongly and negatively associated (r = –0.79 to –0.89, p < 0.01) with the waist-to-hip ratio but not with total adiposity. In conclusion, these results demonstrate the existence of site differences in adipose tissue insulin action in morbidly obese women. The greater insulin effect on glucose transport in round ligament adipocytes was associated with a higher expression of GLUT4 when compared to subcutaneous abdominal and omental fat cells. Moreover, despite the regional variation in GLUT4 expression, an increased proportion of abdominal fat was found to be associated with lower levels of GLUT4 in all adipose regions investigated. [Diabetologia (1997) 40: 590–598] Received: 8 October 1996 and in revised form: 28 January 1997     

Metabolism of adipose tissue in intraabdominal depots in severely obese men and women

In groups of obese men and women with an abdominal type of fat distribution, we measured fat cell size, lipoprotein lipase (LPL) activity and lipolysis stimulated by norepinephrine (NE) or isoproterenol (ISO) or inhibited by insulin, in subcutaneous abdominal and retroperitoneal (nonportal), as well as in omental and mesenteric (portal) adipose tissues. Both men and women had large intraabdominal adipocytes. No differences were found between the two groups of obese subjects in fat cell size or LPL activity in the different adipose tissue regions. Women had as high NE- or ISO-stimulated lipolysis in the portal as in nonportal fat tissues, equally high as that found in men. In comparisons with a previous study in nonobese men and women, these results show an increased fat cell size in all tissues in obese women and an increased lipolysis in portal tissues in obese women and in nonportal tissues in obese men. Taken together, these results might mean that obese men and abdominally obese women have a large potential to release free fatty acids (FFA) from intraabdominal depots. This might be followed by metabolic derangements seen in such groups of obese subjects.     

Mesenteric adipose tissue alterations resulting from experimental reactivated colitis

BACKGROUND: Adipose tissue secretes a large number of hormones that act either locally or at distant sites, modulating immune responses, inflammation, and many endocrine and metabolic functions. Abnormalities of fat in the mesentery have been long recognized in surgical specimens as characteristic features of Crohn's disease; however, the importance of this in chronic inflammatory disease is unknown. Additionally, adipocytes in depots that enclose lymph nodes or other dense masses of lymphoid tissue have many site-specific physiological properties. METHODS: In this study, the alterations of mesenteric and perinodal mesenteric adipose tissue during experimental colitis, induced by repeated intracolonic trinitrobenzene sulfonic acid instillations, were evaluated, focusing on morphological and activity alterations and the adipocytokine production profile. RESULTS: After a 35-day protocol, the colitis animals presented greater mesenteric fat masses despite their lower body weights. Another adipose tissue depot, epididymal adipose tissue, was also evaluated and no change in mass was observed. The mesenteric adipocyte from colitis animals had a reduced diameter, normal PPAR-gamma-2 expression, and higher basal lipolysis and TNF-alpha production when compared to normal rats. Perinodal mesenteric adipocytes present normal diameters, downregulated levels of PPAR-gamma-2, higher basal lipolysis and TNF-alpha, and leptin and adiponectin production. CONCLUSIONS: The findings suggest that mesenteric adipose tissue has a site-specific response during experimental inflammation, where perinodal adipose tissue retains the ability to produce different adipocytokines. These substances may interfere in many lymph node aspects, while mesenteric adipose tissue produces substances that could contribute directly to aggravate the inflammatory process.     

Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes

The mechanisms by which androgens regulate fat mass are poorly understood. Although testosterone has been reported to increase lipolysis and inhibit lipid uptake, androgen effects on proliferation and differentiation of human mesenchymal stem cells (hMSCs) and preadipocytes have not been studied. Here, we investigated whether dihydrotestosterone (DHT) regulates proliferation, differentiation, or functional maturation of hMSCs and human preadipocytes from different fat depots. DHT (0-30 nM) dose-dependently inhibited lipid accumulation in adipocytes differentiated from hMSCs and downregulated expression of aP2, PPARgamma, leptin, and C/EBPalpha. Bicalutamide attenuated DHT's inhibitory effects on adipogenic differentiation of hMSCs. Adipocytes differentiated in presence of DHT accumulated smaller oil droplets suggesting reduced extent of maturation. DHT decreased the incorporation of labeled fatty acid into triglyceride, and downregulated acetyl CoA carboxylase and DGAT2 expression in adipocytes derived from hMSCs. DHT also inhibited lipid accumulation and downregulated aP2 and C/EBPalpha in human subcutaneous, mesenteric and omental preadipocytes. DHT stimulated forskolin-stimulated lipolysis in subcutaneous and mesenteric preadipocytes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots. CONCLUSIONS: DHT inhibits adipogenic differentiation of hMSCs and human preadipocytes through an AR-mediated pathway, but it does not affect the proliferation of either hMSCs or preadipocytes. Androgen effects on fat mass represent the combined effect of decreased differentiation of fat cell precursors, increased lipolysis, and reduced lipid accumulation.     

Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution

Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation. We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic alpha2A-adrenergic receptors in sc adipocytes. The increased number of alpha2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on alpha2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot. These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic alpha2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype alpha. These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic alpha2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.     

Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage

We present multiple findings on derangements in lipid metabolism in type 2 diabetes. The increase in the intracellular deposition of triglycerides (TG) in muscles, liver and pancreas in subjects prone to diabetes is well documented and demonstrated to attenuate glucose metabolism by interfering with insulin signaling and insulin secretion. The obesity often associated with type 2 diabetes is mainly central, resulting in the overload of abdominal adipocytes with TG and reducing fat depot capacity to protect other tissues from utilizing a large proportion of dietary fat. In contrast to subcutaneous adipocytes, the central adipocytes exhibit a high rate of basal lipolysis and are highly sensitive to fat mobilizing hormones, but respond poorly to lipolysis restraining insulin. The enlarged visceral adipocytes are flooding the portal circulation with free fatty acids (FFA) at metabolically inappropriate time, when FFA should be oxidized, thus exposing nonadipose tissues to fat excess. This leads to ectopic TG accumulation in muscles, liver and pancreatic beta-cells, resulting in insulin resistance and beta-cell dysfunction. This situation, based on a large number of observations in humans and experimental animals, confirms that peripheral adipose tissue is closely regulated, performing a vital role of buffering fluxes of FFA in the circulation. The central adipose tissues tend to upset this balance by releasing large amounts of FFA. To reduce the excessive fat outflow from the abdominal depots and prevent the ectopic fat deposition it is important to decrease the volume of central fat stores or increase the peripheral fat stores. One possibility is to downregulate the activity of lipoprotein lipase, which is overexpressed in abdominal relatively to subcutaneous fat stores. This can be achieved by gastrointestinal bypass or gastroplasty, which decrease dietary fat absorption, or by direct means that include surgical removal of mesenteric fat. Indirect treatment consists of the compliant application of drastic lifestyle change comprising both diet and exercise and pharmacotherapy that reduces mesenteric fat mass and activity. The first step should be an attempt to effectively induce a lifestyle change. Next comes pharmacotherapy including acarbose, metformin, PPARgamma, or PPARgammaalpha agonists, statins and orlistat, estrogens in postmenopausal women or testosterone in men. Among surgical procedures, gastric bypass has been proven to produce beneficial results in advance of other surgical techniques, the evidence basis of which still needs strengthening.     

Site-specific and sex differences in the rates of fatty acid/triacylglycerol substrate cycling in adipose, tissue and muscle of sedentary and exercised dwarf hamsters (Phodopus sungorus)

Site-specific and sex differences in fatty acid/triacylglycerol substrate cycling in adipose tissue and muscle were found in vivo in adult hamsters (Phodopus sungorus) fed ad libitum, both at rest and immediately after moderate exercise. In adipose tissue, rates of fatty acid/triacylglycerol cycling at rest were highest in two small intermuscular depots and lowest in the groin, behind forelimb, epididymal and kidney sites. Cycling rates were significantly higher in the groin and in the two depots around the forelimb in females. Following an hour of exercise in a hamster ball, the rates of fatty acid/triacylglycerol cycling rose significantly in the intermuscular and certain superficial adipose fatty depots of both sexes, but the increases were more uniform in males. In females only, cycling rates in the skeletal muscles also increased significantly. The rates of fatty acid/triacylglycerol cycling in adipose tissue correlate closely with the site-specific activities of hexokinase and phosphofructokinase, but not with mean adipocyte volume per se. The data are consistent with the hypotheses that adipose depots are depleted selectively during exercise and that there are sex differences in the pattern of lipid mobilization.     

Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. Because adipose tissue depots differ in the strength of their association with the adverse metabolic consequences of obesity, we studied the secretion of adiponectin in vitro from paired samples of isolated human omental and sc adipocytes and its regulation by insulin and rosiglitazone. Cells were incubated for 12 or 24 h with and without treatment with 100 nM insulin, 8 micro M rosiglitazone, or both combined; adiponectin secreted into the culture medium was measured by a RIA with a human adiponectin standard and normalized for cellular DNA content. Secretion of adiponectin by omental cells was generally higher than sc cells and showed a strong negative correlation with body mass index (r = -0.78;P = 0.013). In contrast, secretion from the sc cells was unrelated to body mass index. Compared with sc-derived adipocytes, adiponectin secretion from omental cells was increased by insulin or rosiglitazone alone and was up to 2.3-fold higher following combined treatment with insulin and rosiglitazone, whereas secretion from sc adipose cells was unaffected by these treatments. These data suggest that reduced secretion from the omental adipose depot may account for the decline in plasma adiponectin observed in obesity. Furthermore, enhanced adiponectin secretion from fat cells derived from the visceral compartment in response to rosiglitazone alone or in combination with insulin may play a role in some of the systemic insulin-sensitizing and antiinflammatory properties of the thiazolidinediones.     

Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes

Visceral adiposity is associated with insulin resistance and type 2 diabetes. This study explores the metabolic differences between s.c. and visceral fat depots with respect to effects in vitro of glucocorticoids and insulin on glucose uptake.Adipocytes from human s.c. and omental fat depots were obtained during abdominal surgery in 18 nondiabetic subjects. Cells were isolated, and metabolic studies were performed directly after the biopsies and after a culture period of 24 h with or without dexamethasone. After washing, basal and insulin-stimulated [14C]glucose uptake as well as cellular content of insulin signaling proteins and glucose transporter 4 (GLUT4) was assessed. Omental adipocytes had an approximately 2-fold higher rate of insulin-stimulated glucose uptake compared with s.c. adipocytes (P < 0.01). Dexamethasone treatment markedly inhibited (by approximately 50%; P < 0.05) both basal and insulin-stimulated glucose uptake in omental adipocytes but had no consistent effect in s.c. adipocytes. The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3-kinase did not differ significantly between the depots, but the expression of protein kinase B (PKB) tended to be increased in omental compared with s.c. adipocytes (P = 0.09). Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes. In contrast, dexamethasone pretreatment had no effect on insulin-stimulated Ser473 phosphorylation of PKB. GLUT4 expression was approximately 4-fold higher in omental than s.c. adipocytes (P < 0.05). Dexamethasone treatment did not alter the expression of GLUT4. In conclusion, human omental adipocytes display approximately 2-fold higher glucose uptake rate compared with s.c. adipocytes, and this could be explained by a higher GLUT4 expression. A marked suppression is exerted by glucocorticoids on glucose uptake and on the expression of insulin signaling proteins in omental but not in s.c. adipocytes. These findings may be of relevance for the interaction between endogenous glucocorticoids and visceral fat in the development of insulin resistance.     

Production and release of macrophage migration inhibitory factor from human adipocytes

BACKGROUND AND AIM OF THE STUDY: Macrophage migration inhibitory factor (MIF) has been identified as a critical mediator of inflammatory responses. Because of its potent migration inhibition activity, it regulates macrophage accumulation in tissues. We therefore analyzed whether human adipocytes produce MIF, in the search of candidate mediators of macrophage infiltration of obese adipose tissue. METHODS: Human adipose tissue samples were obtained from various depots. The precursor cells were allowed to differentiate under defined adipogenic culture conditions. MIF expression was analyzed by RT-PCR, ELISA, and immunocytochemistry. RESULTS: Human preadipocytes secreted MIF in a differentiation-dependent fashion with maximum concentrations at d 12, whereas MIF mRNA was detected in both undifferentiated and differentiated cells at relatively constant levels. Immunocytochemical analysis showed that MIF protein was present in preadipocytes and more pronounced in differentiated adipocytes. Freshly isolated mature adipocytes from sc, omental, and mammary depots released MIF at rates of up to 10,000 pg/ml.24 h. Most importantly, MIF production was positively correlated with donor body mass index. Secretion of MIF was not influenced by lipopolysaccharide, interferon-gamma, or IL-4. The rates of MIF release from sc and omental adipocytes were similar but approximately 10 times higher compared with mammary adipocytes. CONCLUSIONS: Human preadipocytes and mature adipocytes from different depots spontaneously release substantial amounts of MIF. Expression levels were positively associated with donor body mass index. Hence, MIF may be an obesity-dependent mediator of macrophage infiltration of adipose tissue.     

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 μg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.     

Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature.

Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH-deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots.     

Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone, and influence of gender

This study examined the regulation of leptin production by dexamethasone and troglitazone. Subcutaneous and omental adipose tissue was obtained during bariatric surgical procedures (30 women and 16 men; body mass index, 52.5 +/- 1.7 kg/m2, age, 39 +/- 2 yr), and adipocytes were cultured in suspension. Subcutaneous adipocytes from females released significantly more leptin than did omental cells from the same subject (P < 0.05), but basal leptin release was not different in adipocytes from these depots in males. Dexamethasone (0.1 micromol/L) significantly increased leptin release within 24 h from sc (135 +/- 13% of control) and omental (227 +/- 53%) adipocytes of females, but not males. Dexamethasone-stimulated leptin production at 48 h was significantly greater in the omental adipocytes of females (398 +/- 64% of control) than in sc adipocytes of females (207 +/- 21%) or the omental (211 +/- 33%) and sc (180 +/- 23%) adipocytes of males. Troglitazone (10 micromol/L; 48 h) significantly inhibited dexamethasone-stimulated leptin release in sc (57 +/- 10.7% inhibition) and omental adipocytes (134 +/- 26% inhibition). There was no gender-related difference in the effect of troglitazone to inhibit dexamethasone-stimulated leptin release. Troglitazone significantly inhibited basal leptin production from omental adipocytes by 15.0 +/- 5.2%. The effect of dexamethasone and troglitazone to regulate leptin release was mediated through changes in ob gene expression, but did not involve changes in glucose uptake or metabolism to lactate. The data suggest that adipocytes from females are more responsive to the stimulatory effect of dexamethasone in vitro than are adipocytes from males. If adipocytes from females are more responsive to relevant in vivo stimuli for leptin secretion such as insulin or glucose, this could contribute to the gender difference in serum leptin. The data also suggest that leptin release from omental adipocytes may be more responsive to hormonal and nutrient regulation in vivo than are sc adipocytes.     

Ovarian hormone status and abdominal visceral adipose tissue metabolism

We examined abdominal sc and visceral adipose tissue metabolism in a sample of 19 regularly cycling premenopausal women (age 46.3 +/- 3.7 yr) and 10 women with natural menopause or pharmacological ovarian suppression (age 51.1 +/- 9.2 yr). Subcutaneous and visceral (omental, epiploic) adipose tissue biopsies were obtained during abdominal hysterectomies. Body composition and adipose tissue distribution were measured before the surgery by dual x-ray absorptiometry and computed tomography, respectively. Ovarian hormone-deficient women tended to be older (P = 0.08) and were characterized by increased visceral adipose tissue area (P < 0.05). Subcutaneous adipocyte size, lipoprotein lipase (LPL) activity, and basal lipolysis were not significantly different between groups. On the other hand, omental fat cell size was significantly higher in ovarian hormone-deficient women, compared with premenopausal women (P < 0.05). The omental/sc LPL activity ratio and omental adipocyte basal lipolysis were also significantly higher in ovarian hormone-deficient women (P < 0.05 for both comparisons). Significant positive correlations were found between visceral adipose tissue area and omental LPL activity (r = 0.54, P < 0.003), omental adipocyte basal lipolysis (r = 0.66, P < 0.0001), and omental fat cell size (r = 0.81, P < 0.0001). In multivariate analyses, ovarian status was no longer a significant predictor of adipose cell metabolism variables after visceral adipose tissue area was entered into the model, with the exception of the omental/sc LPL activity ratio, which remained independently associated with ovarian status. In conclusion, although the size of the visceral adipose tissue compartment was an important determinant of adipocyte metabolism in this depot, the increased omental/sc LPL activity ratio in ovarian hormone-deficient women supports the notion of a predominant visceral fat storage in these women.