Sympathetic denervation of one white fat depot changes norepinephrine content and turnover in intact white and brown fat depots

It is well-established that the sympathetic nervous system (SNS) regulates adipocyte metabolism and recently it has been reported that sensory afferents from white fat overlap anatomically with sympathetic efferents to white fat. The studies described here characterize the response of intact fat pads to selective sympathectomy (local 6-hydroxydopamine (6OHDA) injections) of inguinal (ING) or epididymal (EPI) fat in male NIH Swiss mice and provide in vivo evidence for communication between individual white and brown fat depots. The contralateral ING pad, both EPI pads, perirenal (PR), and mesenteric (MES) pads were significantly enlarged 4 weeks after denervating one ING pad, but only intrascapular brown adipose tissue (IBAT) increased when both ING pads were denervated. Denervation of one or both EPI pad had no effect on fat depot weights. In an additional experiment, norepinephrine turnover (NETO) was inhibited in ING, retroperitoneal (RP), MES, and IBAT 2 days after denervation of both EPI or of both ING pads. NE content was reduced to 10-30% of control values in all fat depots. There was no relation between early changes in NETO and fat pad weight 4 weeks after denervation, even though the reduction in NE content of intact fat pads was maintained. These data demonstrate that there is communication among individual fat pads, presumably through central integration of activity of sensory afferent and sympathetic efferent fibers, that changes sympathetic drive to white adipose tissue in a unified manner. In specific situations, removal of sympathetic efferents to one pad induces a compensatory enlargement of other intact depots.     

Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In experiment 1, one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice that were then infused for 13 days with PBS or 10 microg leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague-Dawley rats that were infused with 50 microg leptin/day. Leptin had little effect on EPI weight or norepinephrine (NE) content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.     

Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation

Surplus energy is principally stored in white adipose tissue (WAT) as triacylglycerol and mobilized via lipolysis through norepinephrine (NE) released from sympathetic nervous system terminals innervating WAT. We demonstrated that central melanocortin receptor agonism provokes differential sympathetic drives across WAT pads and interscapular brown adipose tissue (IBAT). Here we tested for differential WAT and IBAT sympathetic drive to known lipolytic stimuli {glucoprivation [2-deoxy-D-glucose (2-DG)], cold exposure (5 degrees C), food deprivation (16 h), or both cold exposure and food deprivation} by measuring NE turnover (NETO). Only inguinal WAT NETO significantly increased across all stimuli. Dorsal subcutaneous WAT NETO only increased with glucoprivation. Retroperitoneal WAT NETO increased with glucoprivation, cold and cold + food deprivation, but not by food deprivation. Epididymal WAT NETO was unaffected by glucoprivation but increased with cold, cold + food deprivation or food deprivation, but to a small significant degree. IBAT NETO was unaffected by glucoprivation or food deprivation, but increased with cold and cold + food deprivation. Plasma glucose decreased with food deprivation and increased with 2-DG administration or cold exposure. Plasma glycerol was increased with food deprivation, cold, and their combination but not with 2-DG, whereas plasma free fatty acids increased with food deprivation, cold + food deprivation, and 2-DG. These data show differential sympathetic drive to WAT and BAT for four different lipolytic stimuli, exemplifying the fat pad-specific pattern of WAT sympathetic drive across lipid-mobilizing conditions and emphasizing the need to analyze multiple adipose depots for measures of NETO and likely most measures.     

Leptin selectively reduces white adipose tissue in mice via a UCP1-dependent mechanism in brown adipose tissue

We tested the hypothesis that leptin, in addition to reducing body fat by restraining food intake, reduces body fat through a peripheral mechanism requiring uncoupling protein 1 (UCP1). Leptin was administered to wild-type (WT) mice and mice with a targeted disruption of the UCP1 gene (UCP1 deficient), while vehicle-injected control animals of each genotype were pair-fed to each leptin-treated group. Leptin reduced the size of white adipose tissue (WAT) depots in WT mice but not in UCP1-deficient animals. This was accompanied by a threefold increase in the amount of UCP1 protein and mRNA in the brown adipose tissue (BAT) of WT mice. Leptin also increased UCP2 mRNA in WAT of both WT and UCP1-deficient mice but increased UCP2 and UCP3 mRNA only in BAT from UCP1-deficient mice. These results indicate that leptin reduces WAT through a peripheral mechanism requiring the presence of UCP1, with little or no involvement of UCP2 or UCP3.     

Short photoperiod exposure increases adipocyte sensitivity to noradrenergic stimulation in Siberian hamsters

Siberian hamsters (Phodopus sungorus) exhibit a naturally occurring, reversible seasonal obesity with body fat peaking in long "summerlike" days (LDs) and reaching a nadir in short "winterlike" days (SDs). These SD-induced decreases in adiposity are mediated largely via sympathetic nervous system (SNS) innervation of white adipose tissue (WAT), as indicated by increased WAT norepinephrine (NE) turnover. We examined whether SDs also increase sensitivity to NE-stimulated lipolysis. This was accomplished by measuring NE- and beta3-adrenoceptor (beta3-AR) agonist (BRL-37344)-induced lipolysis (glycerol release) as well as NE-induced cAMP accumulation by inguinal, epididymal, and retroperitoneal WAT (IWAT, EWAT, and RWAT) in isolated adipocytes of LD- and SD-housed hamsters. SDs increased potency/efficacy of NE-triggered lipolysis in a temporally and fat pad-specific manner. Thus when WAT pad mass decreased most rapidly (5 wk of SDs), potency (sensitivity/EC50) and efficacy (maximal response asymptote) of NE-stimulated lipolysis were increased for all WAT pads and also at 10 wk for IWAT compared with their LD counterparts. SD enhancement of lipolysis was similar for NE and BRL-37344 in IWAT adipocytes. These results, coupled with our previous demonstration that SDs upregulate WAT beta3-AR mRNA expression, suggest that increased beta3-ARs mediated the SD-induced increased NE sensitivity. NE-stimulated adipocyte accumulation of cAMP was greater after 5 wk of SDs for IWAT and EWAT and after 10 wk of SDs for IWAT compared with LDs, with no photoperiod effect for RWAT. Therefore, the SD-induced increase in SNS drive to WAT and increased sensitivity to this drive may work together to increase lipolysis in SDs.     

Direct and indirect effects of leptin on adipocyte metabolism

Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

High lipolytic activity and dyslipidemia in a Spontaneous Hypertensive/NIH Corpulent (SHR/N-cp) rat: a genetic model of obesity and type 2 diabetes mellitus

In order to better understand the link between obesity and type 2 diabetes, lipolysis and its adrenergic regulation was investigated in various adipose depots of obese adult females SHR/N-cp rats. Serum insulin, glucose, free fatty acids (FFA), triglycerides (TG) and glycerol were measured. Adipocytes were isolated from subcutaneous (SC), parametrial (PM) and retroperitoneal (RP) fat pads. Total cell number and size, basal lipolysis or stimulated by norepinephrine (NE) and BRL 37344 were measured in each depot. Obese rats were hyperinsulinemic and hyperglycemic, suggesting high insulin resistance. They presented a marked dyslipidemia, attested by increased serum FFA and TG levels. High serum glycerol levels also suggest a strong lipolytic rate. Obese rats showed an excessive development of all fat pads although a more pronounced effect was observed in the SC one. The cellularity of this depot was increased 8 fold when compared to lean rats, but these fat cells were only 1.5 to 2-fold larger. SC adipocytes showed a marked increase in their basal lipolytic activity but a lack of change in responsiveness to NE or BRL 37344. The association between high basal lipolysis and increased cellularity yields to a marked adipose cell lipolytic rate, especially from the SC region. SHR/N-cp rats were characterized by a hyperplasic type of obesity with an excessive development of the SC depot. The dyslipidemia, attested by an altered serum lipid profile could be attributed to excessive lipolysis that contributes to increased FFA levels, and to early development of insulin resistance through a lipotoxicity effect.     

Growth Hormone Treatment of Hypophysectomized Rats Increases Catecholamine-induced Lipolysis and the Number of β-Adrenergic Receptors in Adipocytes: No Differences in the Effects of Growth Hormone on Different Fat Depots

Growth hormone (GH) has a lipolytic effect in adipose tissue but this effect may differ in adipose tissue from various fat depots. This latter possibility was investigated in the present study, in which the effects of GH in vivo on catecholamine-induced lipolysis and the number of β-adrenergic receptors in isolated adipocytes from different fat depots of hypophysectomized rats were investigated. Female and male Sprague-Dawley rats were hypophysectomized or sham-operated at 45 days of age. One week after the operation, hormonal replacement therapy with L-thyroxine and hydrocortisone acetate was given. In addition, groups of rats were treated with GH (1.33 mg/kg per day, given as two daily subcutaneous injections). After 1 week of hormonal treatment, adipocytes were isolated from the parametrial, epididymal and inguinal fat pads, and glycerol release after catecholamine-stimulation and ¹²⁵I-cyanopindolol binding were measured. Hypophysectomy resulted in a marked decrease in the lipolytic response to catecholamines. GH treatment significantly increased catecholamine-induced lipolysis with similar effects in adipocytes from parametrial or epididymal and inguinal fat depots in both female and male rats. There were no differences between norepinephrine compared with isoproterenol-induced responses. ¹²⁵I-cyanopindolol binding was reduced after hypophysectomy and normalized by GH treatment, without differences between parametrial and inguinal adipose tissue regions. We conclude that the lipolytic effects of GH in the rat may partly be mediated by a stimulatory effect on β-adrenergic receptors in adipocytes. In addition, GH exerted similar effect on catecholamine-induced lipolysis and β-adrenergic receptors in adipocytes from parametrial, epididymal and inguinal fat depots.     

Relationships among serum triacylglycerol, fat pad weight, and lipolysis in iron-deficient rats

We studied the relationships among serum triacylglycerol (TG), fat pad weight, and lipolytic response to norepinephrine (NE) in iron-deficient rats. We used male Sprague-Dawley International Golden Standard rats. The rats were randomly divided into four groups: two iron-adequate groups for 1 week (1A) and 5 weeks (5A), and two iron-deficient groups for 1 week (1D) and 5 weeks (5D), based on the AIN-93G diet. Iron-deficient treatment caused a significant decrease in hemoglobin (Hb) and hematocrit (Hct) values and an increase in relative heart weight in 1D and 5D rats. Although serum TG was not affected by the 1-week iron-deficient treatment, it was significantly increased by 5-week iron-deficient treatment. The 1-week iron-deficient treatment significantly decreased the relative weight of the retroperitoneal fat pads, but not that of the epididymal fat pads. On the other hand, the 5-week iron-deficient treatment significantly decreased the relative weight of both fat pads; the degree of decrease was 41% and 32% for retroperitoneal and epididymal fat pads, respectively. Basal lipolysis significantly decreased in the epididymal adipocytes from 1D rats, whereas lipolytic response to NE markedly increased. No effect due to the 5-week treatment on basal lipolysis was observed in either retroperitoneal or epididymal adipocytes. In addition, lipolytic response to NE significantly increased in the retroperitoneal, but not the epididymal adipocytes. These results demonstrate that the effects of an iron-deficient diet on fat pad weight are different, depending on the duration of the treatment and the location of fat pads. In addition, iron deficiency-caused hypertriacylglycerolmia may be predominantly related to the increase in lipolysis in retroperitoneal rather than in epididymal adipocytes. The data further show that the increase in lipolysis of epididymal adipocytes occurs in the earlier stage prior to a severe iron-deficient state.     

Lipid metabolism of monosodium glutamate obese rats after partial removal of adipose tissue

We analyzed the effects of partial fat pad removal on retroperitoneal and epididymal fat depots and carcass metabolism of control (C) and MSG-obese (M) rats. Three-month-old C and M male Wistar rats were submitted to either partial surgical excision of epididymal and retroperitoneal fat tissue (lipectomy, L) or sham surgery (S) and studied after 7 or 30 days. Retroperitoneal and epididymal tissue re-growth after lipectomy was not observed, as indicated by the low pads weight of the L groups. The lipolysis rate was stimulated in LC7 and LM7, probably due to surgical stress and low insulin levels. In LM7, but not in LC7, in vivo lipogenesis rate increased in retroperitoneal and epididymal fat tissue, as did the diet-derived lipid accumulation in epididymal fat tissue. Although these local increases were no longer present in LM30, this group showed a large increase in the percentage of small area adipocytes in both pads as well as increased carcass lipogenesis rate. The present data showed that the partial removal of fat depots affected the metabolism of control and MSG-obese rats differently. In the obese animals only, it stimulated both local and carcass lipogenesis rate as well as adipocyte differentiation, i.e. responses likely to favor excised tissue re-growth and/or compensatory growth of non-excised depots.     

Alteration of rat adipose tissue lipolytic response to norepinephrine by dietary fatty acid manipulation.

The present study clearly shows that, by feeding rats a semi-synthetic diet of known composition enriched with saturated fatty acids, the epididymal fat pad responsiveness to norepinephrine $\text{in}\text{vitro}$ can be abolished relative to fat pads from animals fed a similar diet but enriched with polyunsaturated fatty acids. Addition of varying concentrations of norepinephrine to the incubation medium produced a clear dose-response relationship in fat pads from animals fed diet enriched with polyunsaturated fatty acids while no effect of norepinephrine was apparent at any dose level in fat tissue from animals fed saturated fatty acids. These changes in lipolytic responsiveness were concurrent with alterations in fatty acid compositions of adipose tissue phospholipids and triglycerides as well as in total tissue contents of phospholipids and cholesterol.     

Effects of neonatal handling on sympathoadrenal activity and body composition in adult male rats

Neonatal handling permanently alters the hypothalamic-pituitary-adrenal (HPA) response to stress. Because the sympathetic nervous system (SNS) and adrenal medulla also participate in stress responses, the impact of daily handling between birth and weaning on SNS and adrenal medullary function was examined in adult rats using techniques of [(3)H]norepinephrine ([(3)H]NE) turnover and urinary catecholamine excretion. Handled animals exhibited a 23% reduction in [(3)H]NE turnover in heart and a 53% decrease in spleen. [(3)H]NE turnover in brown adipose tissue, stomach, and kidney did not differ between handled and nonhandled animals. In contrast, urinary epinephrine (Epi) excretion was significantly greater in handled rats in response to a 3-day fast than in nonhandled animals. Although body weight, weight gain in response to dietary enrichment with sucrose or lard, or body fat content did not differ in handled and nonhandled animals, handled rats displayed heavier abdominal fat depots than nonhandled animals, implying a difference in body fat distribution. Neonatal handling thus leads to decreased sympathetic activity within specific subdivisions of the SNS and, by contrast, to increased adrenal medullary responsiveness.     

Lipolysis in Intraabdorninal Adipose Tissues of Obese Women and Men

Intraabdominal fat in humans is located in two major depots, the omental and mesenteric. We compared basal and stimulated lipolysis in adipose tissue from these two depots and the subcutaneous abdominal depot of obese women and men. Omental fat cells of women are smaller and have lower rates of basal lipolysis than in men. Basal Iipolysis rates are significantly higher in subcutaneous than intraabdominal adipose tissues of both genders. In men, the incremental lipolytic response to norepinephrine is significantly greater in both intraabdominal fat depots than in the subcutaneous fat, while in women tlie response of tlie mesenteric is lower than tlie omental. In women, but not men, responsiveness to tlie beta agonist isoproterenol is also increased in omental tissue. Thus, in women, omental and mesenteric adipose tissues show distinctly different metabolic properties which may moderate the impact of intraabdominal obesity.     

Thermogenic and metabolic consequences of thyroid hormone treatment in brown and white adipose tissue

Male rats were treated with triiodothyronine in the drinking water for 12 days. In vitro rates of isoprenaline stimulated lipolysis were significantly greater in brown but not white adipose tissue. Rates of [¹⁴C]glucose incorporation into triacylglycerols were significantly reduced in BAT (brown adipose tissue) and WAT (white adipose tissue) under basal and isoprenaline stimulated conditions, in a second experiment, hyperthyroid animals showed impaired weight gain, despite increased food intake during t9 days' treatment. Energy expenditure on days 5 and 12, and BAT core temperature differences (TBAT - T_CORE) on day 19, were significantly greater than in control animals. Epididymal white fat pad weight was reduced and interscapular brown fat pad weight increased by triiodothyronine treatment.     

Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels

Transgenic mice overexpressing leptin (LepTg) exhibit substantial reductions in adipose mass. Since the binding of leptin to its receptor activates the sympathetic nervous system, we reasoned that the lean state of the LepTg mice could be caused by chronic lipolysis. Instead, the LepTg mice exhibited a low basal lipolysis state and their lean phenotype was not dependent on the presence of beta3-adrenergic receptors. In their white adipose tissue, protein levels of protein kinase A, hormone-sensitive lipase, and ADRP were not impaired. However, compared to normal mice, perilipin, perilipin mRNA, and cAMP-stimulated PKA activity were significantly attenuated. Overall, we demonstrate that the lean phenotype of the LepTg mice does not result in a chronically elevated lipolytic state, but instead in a low basal lipolysis state characterized by a decrease in perilipin and PKA activity in white fat.     

NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines

The sympathetic nervous system plays a central role in lipolysis and the production of leptin in white adipose tissue (WAT). In this study, we have examined whether nerve growth factor (NGF), a target-derived neurotropin that is a key signal in the development and survival of sympathetic neurons, is expressed and secreted by white adipocytes. NGF mRNA was detected by RT-PCR in the major WAT depots of mice (epididymal, perirenal, omental, mesenteric, subcutaneous) and in human fat (subcutaneous, omental). In mouse WAT, NGF expression was observed in mature adipocytes and in stromal vascular cells. NGF expression was also evident in 3T3-L1 cells before and after differentiation into adipocytes. NGF protein, measured by ELISA, was secreted from 3T3-L1 cells, release being higher before differentiation. Addition of the sympathetic agonists norepinephrine, isoprenaline, or BRL-37344 (beta(3)-agonist) led to falls in NGF gene expression and secretion by 3T3-L1 adipocytes, as did IL-6 and the PPARgamma agonist rosiglitazone. A substantial decrease in NGF expression and secretion occurred with dexamethasone. In contrast, LPS increased NGF mRNA levels and NGF secretion. A major increase in NGF mRNA level (9-fold) and NGF secretion (相似文献   

Direct innervation of white fat and adrenal medullary catecholamines mediate photoperiodic changes in body fat

Seasonal adjustments in Siberian hamster adiposity are triggered by day length changes [i.e., short "winter-like" days (SDs) elicit body fat decreases vs. long "summer-like" days (LDs)]. These and other white adipose tissue (WAT) mass decreases traditionally have been ascribed to lipolysis triggered by sympathetically mediated, adrenal medullary released epinephrine; however, recent evidence suggests that direct sympathetic innervation of WAT also is important. Therefore, the contributions of WAT sympathetic innervation and adrenal medullary catecholamines to SD-induced decreases in adiposity were tested. Siberian hamsters were surgically bilaterally adrenal demedullated (ADMEDx) or sham ADMEDx, and all had one inguinal WAT (IWAT) pad sympathectomized via locally injected guanethidine, with the contralateral pad serving as a within-animal innervated control. One-half of the hamsters remained in LDs; the remainder was transferred to SDs. Guanethidine and ADMEDx abolished IWAT norepinephrine and adrenal epinephrine contents, respectively. Although sympathetic denervation or ADMEDx alone did not block SD-induced decreases in IWAT mass, their combination did. These results suggest that both adrenal catecholamines and the sympathetic innervation of WAT interact to decrease SD-induced decreased adiposity.     

Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake

Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783-R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding.     

Obesity is induced in mice heterozygous for cyclooxygenase-2.

In mice heterozygous for the cyclooxygenase-2 gene (COX-2+/-) the body weight was enhanced by 33% as compared to homozygous COX-2-/- mice. The weights of the gonadal fat pads in COX-2+/- mice were enhanced by 3.5 to 4.7 fold as compared to COX-2-/- mice and by 1.5 to 3.5 fold as compared to wild-type controls+/+ Serum leptin levels and leptin release by cultured adipose tissue of COX-2+/- mice were both elevated as compared to either control or COX-2-/- animals. The basal release of PGE2 or 6 keto PGF1alpha per fat pad over a 24 h incubation of adipose tissue was reduced by 80% and 95% respectively in tissue from COX-2-/- mice. NS-398, a specific COX-2 inhibitor, inhibited leptin release by 27% in adipose tissue from control mice, 31% in tissue from COX-1-/- mice and by 23% in tissue from COX-2+/- mice while having no effect on leptin release by adipose tissue from COX-2-/- mice. These data indicate that heterozygous COX-2 mice develop obesity which is not secondary to a defect in leptin release by adipose tissue.     

Non-shivering thermogenesis and obesity in adult diabetic Wistar fatty rats

1. Characteristics of resting and of norepinephrine (NE)-stimulated thermogenesis, and the glycemic response to NE were determined in adult male Wistar Fatty rats. Rats were maintained on Purina chow No. 5001 until 22 weeks of age, and fed semisynthetic diets containing 54% carbohydrate, 20% protein, 16% mixed fats, plus essential vitamins, minerals, and non-nutritive fiber from 22 until 30 weeks of age. 2. Obese rats were 50% heavier than lean throughout the study. Phenotype effects (obese greater than lean) were present for retroperitoneal (RP) and dorsal (DOR) white fat depot weight, adipocyte number per depot, and adipocyte lipid content. Epididymal mass and cellularity were similar in both phenotypes. 3. Interscapular brown adipose tissue (IBAT) mass, adipocyte size, and adipocyte number were greater in obese than in lean. Resting metabolic rates (RMR) of obese rats were lower than in lean, and increased 79% in lean but only 33% in obese animals following NE (200 micrograms/kg BW, s.c.) stimulation. 4. The glycemic response to NE occurred normally in both phenotypes, and resulted in a 3-fold increment in plasma glucose in lean rats and a 5-6-fold increase in plasma glucose in obese rats. 5. The results of this study are consistent with hyperplasia and hypertrophy of IBAT, RP and DOR depots, and indicate that the capacity for non-shivering thermogenesis is impaired in the obese phenotype of this strain in spite of peripheral sensitivity to NE and greater mass and cellularity of brown adipose tissue.