Effects of Testosterone on Triglyceride Uptake and Mobilization in Different Adipose Tissues in Male Rats in Vivo

LI, MIN AND PER BJ4OURNTORP. Effects of testosterone on triglyceride uptake and mobilization in different adipose tissues in male rats in vivo. Obes Res. 1995;3:113–119. The effects of testosterone (T) on uptake and mobilization of orally administered triglyceride were examined in male rats. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo. (U-14 C) oleic acid in sesame oil was given by gastric gavage to male, sham operated, castrated and castrated + T substituted rats, and accumulation and half-life of radioactivity measured. In castrated rats in comparisons with sham-operated and castrated + T rats, serum T was absent, and body weight lower (P< 0.05 or 0.01), but adipocytes in retroperitoneal and mesenteric tissues became significantly heavier. Radioactivity (dpm/mg triglyceride) was higher, in retroperitoneal tissue at 4 hours, 7, 30 days, and in mesenteric tissue at 4 hours, and at 30 and 60 days after oral label administration (0.1 > p > 0.05 or P< 0.05), no differences were seen in epididymal or inguinal depots at 4 hours. When radioactivity was expressed per adipocyte, the castrated group showed significantly higher radioactivity when compared to sham and castrated + T groups at 7 and 30 days in retroperitoneal and at 60 days in mesenteric adipocytes (P< 0.05 or 0.01). Half life (T 1/2) of radioactivity was longer in mesenteric tissue in the castrated rats than the other two groups (sham group, 33 days ± 2; castrated group, 58 days ± 6; and castrated + T group, 39 days ± 3, P< 0.05), but there were no differences between groups in retroperitoneal adipose tissue. It was concluded that T exerts important, multiple effects on triglyceride storage and mobilization in adipose tissue, with regional differences between adipose tissues.     

Resistin expression in different adipose tissue depots during rat development

Resistin is a hormonal factor synthesised by adipocytes that was first thought to be related with the resistance to insulin in obesity, but whose function is not yet completely established. Here we have studied the ontogenic pattern of resistin mRNA expression in different white adipose tissue depots (WAT) – epididymal, inguinal, mesenteric and retroperitoneal – and in brown adipose tissue (BAT), as well as the circulating resistin levels, in rats of different ages (from the suckling period to one year of age). Resistin mRNA was determined by Northern blotting, and serum levels by enzyme immunoassay. In WAT, resistin expression remains almost constant with age, except in early development, where there is a peak of expression in the epididymal and retroperitoneal depots, and a decrease in the inguinal one, while the expression remains constant for the mesenteric depot. Moreover, there is a site-specific difference regarding resistin expression: all the depots express characteristic levels of mRNA, especially at the age of 2 months, the moment when resistin mRNA levels are significantly higher in the epididymal and the retroperitoneal than in the inguinal and mesenteric WAT and than in the BAT. The transient increased resistin expression in the epididymal and the retroperitoneal WAT at a period of time in which there is a change in diet (from milk to chow) suggests a common nutritional regulation of the resistin gene. Circulating resistin levels increase with age probably reflecting the increase in the body fat content.     

Heterogeneity among white adipose tissue depots in male C57BL/6J mice

The widespread prevalence of obesity has lead to extensive research on white adipose tissue (WAT), which frequently uses the C57BL/6J mouse strain as a model. In many studies, results obtained in one WAT depot are often extrapolated to all WAT. However, functional differences among WAT depots are now becoming apparent. Thus, to identify the molecular mechanisms responsible for WAT depot-specific differences under "normal" conditions, four C57BL/6J mouse WAT depots (inguinal, mesenteric, epididymal, and retroperitoneal) were analyzed. Depot proteomic profiles, along with weights, protein contents, adipocyte sizes and oxidative stress were determined. Mesenteric WAT had almost twice the protein content of the other depots analyzed. Mean adipocyte size was highest in epididymal and lowest in mesenteric and inguinal depots. The proteome of inguinal WAT displayed low levels of enzymes involved in ATP generation, glucose and lipid metabolism, and antioxidant proteins. Higher levels of these proteins were observed in mesenteric and epididymal WAT, with variable levels in the retroperitoneal depot. Some of these proteins showed depot-specific correlations with plasma levels of insulin, leptin, and adiponectin. In agreement with the proteomic data, levels of the antioxidant protein heat shock protein β1 (HSPβ1) also were lower in inguinal WAT when analyzed by western blotting and immunohistochemistry. Also, lipid peroxidation products showed similar trends. Our results are consistent with lower triglyceride turnover and lower oxidative stress in inguinal than mesenteric and epididymal WAT. The observed WAT depot-specific differences provide clues as to the mechanisms leading to these depots' respective diverse functions.     

Triglyceride Uptake in Muscles in Rats

Exogenous lipid is assimilated with different priorities in adipose tissue regions and varies in the fasting and fed conditions. The quantitative role of uptake of lipid in muscle has not been evaluated. In order to examine the uptake in other than adipose tissues, U¹⁴C-oleic acid in sesame oil was administered orally to conscious rats, and lipid label measured after different times in serum, heart, liver, mesenteric, retroperitoneal, inguinal and epididymal fat pads, as well as in red and white parts of gastrocnemius, extensor digitorum longus and soleus muscles. Lipid uptake in total adipose tissue was calculated from dissected adipose tissues plus lipids extracted from the eviscerated, skinned carcass. Lipid uptake in total muscle tissue was estimated from label in dissected muscles plus that in the carcass, assuming similar intracellular lipid contents and radioactivity as that averaged from dissected muscles. Lipid uptake in the liver was calculated from directly extracted lipid. Four hours after lipid administration to fed rats lipid radioactivity in heart and serum was minimal and had essentially disappeared at 8 hours. Liver label declined rapidly from peak values at or before 4 hours. Adipose tissue radioactivity increased gradually up to 16 hours and then decreased. Label in muscles was highest at 4 hours in the red gastrocnemius, and then decreased, while the other muscles showed a constant radioactivity over the observation period (24 hours). Radioactivity expressed per unit muscle mass seemed to be proportional to the oxidative capacity of muscles. In comparisons between fed and fasted rats at 16 hours, when adipose tissue label peaked, liver, individual muscles and carcass did not show any significant differences while adipose tissue label was fivefold higher in fed than fasted rats. The distribution of total measured lipid radioactivity between total adipose tissue, total muscle tissue and liver in fed rats at this time-point was 76. 8, 14. 4 and 8. 8% respectively, and in the fasted state 26. 4, 51. 6 and 22. 0%. These estimations suggest that lipid uptake in the fed state is dominated by adipose tissue, while in the fasted state the lipid uptake is higher in muscles than adipose tissues. It was concluded that uptake of absorbed, exogenous triglyceride in muscle is of significance, particularly in the fasted state. This lipid has a half life of several days. It is suggested that this lipid is oxidized in situ, contributing with a hidden fraction to lipid energy needs, or partially transferred to adipose tissue. Lipid uptake in muscle probably constitutes a significant fraction of assimilated exogenous lipid, particularly in the fasting state.     

The PPARγ agonist rosiglitazone promotes the induction of brite adipocytes,increasing β-adrenoceptor-mediated mitochondrial function and glucose uptake

Recruitment and activation of brite (or beige) adipocytes has been advocated as a potential avenue for manipulating whole-body energy expenditure. Despite numerous studies illustrating the differences in gene and protein markers between brown, brite and white adipocytes, there is very little information on the adrenergic regulation and function of these brite adipocytes. We have compared the functional (cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, extracellular acidification rates, calcium influx) profiles of mouse adipocytes cultured from three contrasting depots, namely interscapular brown adipose tissue, and inguinal or epididymal white adipose tissues, following chronic treatment with the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone. Prototypical brown adipocytes readily express β₃-adrenoceptors, and β₃-adrenoceptor stimulation increases cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, and extracellular acidification rates. Treatment of brown adipocytes with rosiglitazone increases uncoupling protein 1 (UCP1) levels, and increases β₃-adrenoceptor mitochondrial function but does not affect glucose uptake responses. In contrast, inguinal white adipocytes only express UCP1 and β₃-adrenoceptors following rosiglitazone treatment, which results in an increase in all β₃-adrenoceptor-mediated functions. The effect of rosiglitazone in epididymal white adipocytes, was much lower compared to inguinal white adipocytes. Rosiglitazone also increased α₁-adrenoceptor mediated increases in calcium influx and glucose uptake (but not mitochondrial function) in inguinal and epididymal white adipocytes. In conclusion, the PPARγ agonist rosiglitazone promotes the induction and function of brite adipocytes cultured from inguinal and epididymal white adipose depots.     

Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein.     

Effects of Dexamethasone on Primarily Cultured Newly Differentiated Rat Adipocytes from Different Adipose Tissue Regions

The effects of dexamethasone (dex) on newly differentiated adipocytes in primary culture derived from mesenteric, retroperitoneal, epididymal, and inguinal subcutaneous adipose tissues of male rats were studied. The degree of differentiation was similar in these adipose precursor cells derived from different regions as assessed by lipoprotein lipase (LPL) activity, an early marker of adipocyte differentiation. LPL activity was increased by addition of dex, and no differences in degree of activation were observed in cells from different adipose tissue regions. Development of both basal and isoproterenol-stimulated lipolysis was also similar in adipose precursor cells from different adipose tissue regions. Dex addition enhanced the isoproterenol-stimulated lipolysis with no regional differences. Studies of binding of [³H]-dex showed no regional differences in either binding affinity or maximal binding capacity. It is concluded that dex stimulates both LPL activity and lipolytic activity in newly differentiated rat adipocytes in primary culture. This seems, however, not to vary in magnitude in cells obtained from different adipose tissue regions. This might be due to the apparent similarity of number and affinity of glucocorticoid binding sites. Regional variations in glucocorticoid regulated LPL and lipolytic activity in adipose tissue might therefore not be due to inherent differences between adipocytes.     

The gender- and fat depot-specific regulation of leptin, resistin and adiponectin genes expression by progesterone in rat

Progesterone affects lipid metabolism in adipose tissue and influences fat distribution in human. The aim of the study was to analyze the effect of progesterone on rat body and fat mass and on expression of genes encoding adipokines involved in the regulation of energy homeostasis. The results presented here indicate that progesterone administration to females caused increase in body and inguinal white adipose tissue mass. The increase of inguinal white adipose tissue mass is associated with the hypertrophy of adipocyte. The same dose of progesterone caused increase of its circulating concentration in males, however it barely reached the value observed in non-treated control females and did not have any effect on body and fat mass. The elevated circulating progesterone concentration was associated with an approximately 6- and 2-fold increase of leptin and resistin mRNA level respectively, and 2-fold decrease of adiponectin mRNA level only in inguinal white adipose tissue of females. RU 486, specific antagonist of progesterone receptor, abolished the effect of progesterone on the adipokine mRNA level in inguinal adipose tissue. In males, the elevated circulating progesterone concentration showed no effects on leptin, resistin or adiponectin mRNA level in inguinal, retroperitoneal or epididymal adipose tissue. Moreover, the results presented in this paper demonstrate a relatively high level of progesterone receptor mRNA in inguinal white adipose tissue of females, which was down-regulated in response to progesterone administration. In retroperitoneal adipose tissue of control females progesterone receptor mRNA level was approximately 3-fold lower as compared to inguinal adipose tissue. In inguinal, epididymal and retroperitoneal white adipose tissue of males progesterone receptor mRNA was hardly detected. Our results suggest that depot- and sex-dependent responsiveness of adipose tissue to the pharmacological dose of progesterone is controlled by both circulating concentration of progesterone and the white adipose tissue progesterone receptor level.     

Retinoids and retinoid-binding protein expression in rat adipocytes.

Adipose tissue has been reported to contain relatively high levels of the specific mRNA for retinol-binding protein (RBP) (Makover A., Soprano, D.R., Wyatt, M. L., and Goodman, D.S. (1989) J. Lipid Res. 30, 171-180). Studies were conducted to explore retinoid and retinoid-binding protein storage and metabolism in adipose tissue. In these studies, we measured RBP and cellular retinol-binding protein (CRBP) mRNA levels and retinoid levels in 6 adipose depots in male rats. Total RNA was isolated from inguinal, dorsal, mesenteric, epididymal, perinephric, and brown adipose tissue, and average RBP and CRBP mRNA levels were determined by Northern blot analysis. The relative levels of RBP mRNA in these 6 anatomically different adipose depots averaged, respectively, 6.3, 6.7, 16, 34, 37, and 21% of the level in a rat liver RNA standard. Retinoid levels in the 6 depots were similar and averaged approximately 6-7 micrograms of retinol eq/g of adipose tissue. Since adipose tissue contains several cell types, the cellular localizations of RBP and CRBP expression and retinoid storage were examined. RNA was prepared from isolated rat adipocytes and stromal-vascular cells. Cellular levels of the mRNAs for RBP, CRBP, apolipoprotein E (apoE), lipoprotein lipase, adipocyte P2, and adipsin were measured by Northern blot analysis. RBP was expressed almost exclusively in the adipocytes and only weakly in the stromal-vascular cells. Both CRBP and apoE mRNA levels were relatively high in the stromal-vascular cell preparations and only very low mRNA levels were found in the adipocytes. Lipoprotein lipase, adipsin, and adipocyte P2 mRNAs were found in substantial levels in both the adipocytes and stromal-vascular cells, but with higher levels present in the adipocytes. Cultured adipocytes synthesized RBP protein and secreted it into the medium. Only adipocytes (not stromal-vascular cells) contained retinol, at levels between 0.65-0.8 micrograms of retinol eq/10(6) cells. These studies demonstrate that adipocytes store retinoid and synthesize and secrete RBP, and suggest that rat adipocytes may be dynamically involved in retinoid storage and metabolism.     

The components required for amino acid neurotransmitter signaling are present in adipose tissues

The adipocyte does not only serve as fuel storage but produces and secretes compounds with modulating effects on food intake and energy homeostasis. Although there is firm evidence for a centrally mediated regulation of adipocyte function via the autonomous nervous system, little is known about signaling between adipocytes. Amino acid neurotransmitters are candidates for such paracrine signaling. Here, we applied immunohistochemistry to detect components required for amino acid transmitter signaling in rat fat depots. In interscapular brown adipose tissue as well as in interscapular, mesenteric, perirenal, and epididymal white adipose tissues, we demonstrate robust immunosignals for the excitatory neurotransmitter glutamate, the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and the GABA-synthesizing enzyme glutamate decarboxylase (GAD) isoforms GAD65 and GAD67. Moreover, all adipose tissues stained for the vesicular glutamate transporter VGLUT1 and the vesicular GABA transporter VGAT in addition to the vesicle marker synaptophysin. Electron microscopic immunocytochemistry showed that VGLUT1 and VGAT, but not VGLUT2 or VGLUT3, are localized in vesicular organelles in adipocytes. The receptors for glutamate (subunits GluR2/3 and NR1 but not mGluR2) and for GABA (GABA(A)Ralpha2) were present in the adipocytes. The presence of glutamate, GABA, their vesicular transporters, and their receptors indicates a paracrine signaling role for amino acids in adipose tissues.     

Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats

The aim of this study was to investigate the role of dietary macronutrient content on adiposity parameters and adipocyte hypertrophy/hyperplasia in subcutaneous and visceral fat depots from Wistar rats using combined histological and computational approaches. For this purpose, male Wistar rats were distributed into 4 groups and were assigned to different nutritional interventions: Control group (chow diet); high-fat group, HF (60% E from fat); high-fat-sucrose group, HFS (45% E from fat and 17% from sucrose); and high-sucrose group, HS (42% E from sucrose). At day 35, rats were sacrificed, blood was collected, tissues were weighed and fragments of different fat depots were kept for histological analyses with the new softwareAdiposoft. Rats fed with HF, HFS and HS diets increased significantly body weight and total body fat against Control rats, being metabolic impairments more pronounced on HS rats than in the other groups. Cellularity analyses usingAdiposoft revealed that retroperitoneal adipose tissue is histologically different than mesenteric and subcutaneous ones, in relation to bigger adipocytes. The subcutaneous fat pad was the most sensitive to the diet, presenting adipocyte hypertrophy induced by HF diet and adipocyte hyperplasia induced by HS diet. The mesenteric fat pad had a similar but attenuated response in comparison to the subcutaneous adipose tissue, while retroperitoneal fat pad only presented adipocyte hyperplasia induced by the HS diet intake after 35 days of intervention. These findings provide new insights into the role of macronutrients in the development of hyperplastic obesity, which is characterized by the severity of the clinical features. Finally, a new tool for analyzing histological adipose samples is presented.     

Convertible adipose tissue in mice

Summary Ability to express uncoupling protein (UCP) and establish UCP-dependent thermogenesis was analyzed in anatomical areas of mice that are generally considered to be white adipose tissue: mesenterial, perimetral, epididymal, inguinal, and superficial layer of interscapular white adipose tissue. The mice were acclimatized for 1 week to 4° C; the following week they were exposed to cold stress (1 h at-20° C, 2–3 times daily). In such conditions in inguinal adipose tissue, slot-blot analysis detected significant amount of UCP mRNA and lipoprotein lipase mRNA. Immuno-electron-microscopic localization of UCP showed that developed mitochondria of cold-stressed inguinal adipocytes contained UCP in the same amount as uncoupled (UC)-mitochondria of brown adipocytes. Morphological and morphometrical analysis showed that such inguinal adipose tissue appeared as brown adipose tissue. Since in control mice, inguinal adipose tissue was UCP-negative and tissue appeared as white adipose tissue, the duration of this white-to-brown adipose tissue conversion was analyzed. Mice, cold stressed for 1 week, were rewarmed at 28° C and their inguinal adipose tissue was analyzed in comparison with interscapular brown adipose tissue and epididymal white adipose tissue for another 37 days. During that time inguinal adipocytes ceased expressing UCP mRNA; UC-mitochondria in inguinal adipocytes were destroyed and replaced with common, C-mitochondria; and UCP was undetectable immunohistochemically. Adipocytes accumulated lipids, and the tissue morphologically once again resembled white adipose tissue. Described changes showed that besides typical brown and white adipose tissue in mice, there existed a third type of adipose tissue described as convertible adipose tissue.     

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.     

Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues

Mainly from cell culture studies, a series of genes that have been suggested to be characteristic of different types of adipocytes have been identified. Here we have examined gene expression patterns in nine defined adipose depots: interscapular BAT, cervical BAT, axillary BAT, mediastinic BAT, cardiac WAT, inguinal WAT, retroperitoneal WAT, mesenteric WAT, and epididymal WAT. We found that each depot displayed a distinct gene expression fingerprint but that three major types of depots were identifiable: the brown, the brite, and the white. Although differences in gene expression pattern were generally quantitative, some gene markers showed, even in vivo, remarkable depot specificities: Zic1 for the classical BAT depots, Hoxc9 for the brite depots, Hoxc8 for the brite and white in contrast to the brown, and Tcf21 for the white depots. The effect of physiologically induced recruitment of thermogenic function (cold acclimation) on the expression pattern of the genes was quantified; in general, the depot pattern dominated over the recruitment effects. The significance of the gene expression patterns for classifying the depots and for understanding the developmental background of the depots is discussed, as are the possible regulatory functions of the genes.     

Resistance to Aging-Associated Obesity in Capsaicin-Desensitized Rats One Year after Treatment

Previous studies demonstrated reduced weight of abdominal white adipose tissue depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months after treatment. The objective of the present study was to find out whether aging-associated obesity and hyperplasia of retroperitoneal white adipose tissue was prevented in older (13.5 month old) Cap-Des rats, one year after treatment with Cap (done when they were 1.5 months old). The prevalence of obesity is known to increase in rats by this age. Abdominal white adipose tissue depots weighed less in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less). The number of mature white adipocytes was 28% less in the retroperitoneal depot but was not significantly different in the epididymal depot. Adipocyte size was not different. Carcass fat was less, both total and as percent of body weight. Food intake was normal for their reduced body size. The exponential increase in retroperitoneal white adipose tissue weight characteristic of aging rats that are becoming obese was virtually absent in Cap-Des rats. We conclude that lack of function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed in Cap-Des rats, results in an alteration in energy balance conducive to leanness. We suggest that the attenuated age-associated increase in circulating CGRP (derived mainly from capsaicin-sensitive nerves) in the Cap-Des rat results in a lower degree of aging-associated insulin-resistance, hence in a lesser degree of obesity.     

Effect of acute exercise on tissue free fatty acids in untrained rats.

The effects of a single bout of swimming on free fatty acids (FFA) in adipose tissue, heart, skeletal muscle, and serum were examined. Surprisingly, in previously untrained rats, FFA were elevated (P less than 0.001) in epididymal, inguinal, and retroperitoneal adipose depots 48 h after a 2-h swim. FFA in the three fat depots returned to resting levels 96 h after exercise. In heart, soleus, and fast-red fibers of the quadriceps, FFA remained elevated (P less than 0.01) for as long as 72 h after the 2-h swim. Serum FFA were still elevated (P less than 0.001) 96 h after swimming but not after 168 h. These results provide evidence that the rise in FFA is an acute effect of exercise and not a cellular adaptation resulting from daily episodes of lipolysis induced by exercise training. In a separate experiment, involving the adaptive response to endurance exercise, adipocytes from epididymal, inguinal, and retroperitoneal depots were reduced in size (P less than 0.001) to approximately the same degree. These results provide evidence that adipocytes from each depot contribute equally in meeting the energy needs of muscle during repeated bouts of endurance exercise.     

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.     

Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues

We have examined whether GLUT-10 and GLUT-12, members of the Class III group of the recently expanded family of facilitative glucose transporters, are expressed in adipose tissues. The mouse GLUT-12 gene, located on chromosome 10, comprises at least five exons and encodes a 622 amino acid protein exhibiting 83% sequence identity and 91% sequence similarity to human GLUT-12. Expression of the GLUT-12 gene was evident in all the major mouse adipose tissue depots (epididymal, perirenal, mesenteric, omental, and subcutaneous white; interscapular brown). The GLUT-10 gene is also expressed in mouse adipose tissues and as with GLUT-12 expression occurred in the mature adipocytes as well as the stromal vascular cells. 3T3-L1 adipocytes express GLUT-10, but not GLUT-12, and expression of GLUT-12 was not induced by insulin or glucose. Both GLUT-10 and GLUT-12 expression was also found in human adipose tissue (subcutaneous and omental) and SGBS adipocytes. It is concluded that white fat expresses a wide range of facilitative glucose transporters.