Metabolism of Different Adipose Tissues in Vivo in the Rat

To explore regional differences in triglyceride retention in white adipose tissues of growing male rats, the mass of adipocytes from epididymal, retroperitoneal, inguinal, and mesenteric tissues were followed with time. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo and in vitro. (U-¹⁴ C) oleic acid in sesame oil was given by gastric gavage to conscious male and female rats, and accumulation and half-life of radioactivity measured. Lipoprotein lipase activity and lipolysis were studied in vitro. Adipocyte triglyceride mass increased linearly in all the depots during 4 months of observation. The increase in mass was more pronounced in retroperitoneal (0.31 μg) and epididymal (0.30 μg) than in mesenteric (0.11 μg) or inguinal (0.05 μg) adipocytes. In the fed state label from (U-¹⁴C) oleic acid first increased with time in liver, muscle, and adipose tissues. In the liver radioactivity peaked at 4 hours, and was not measurable in either liver or muscle after a time point between 24 hours to 1 week. In contrast label continued to increase in adipose tissues up to about 16 hours to 24 hours, suggesting transfer of label by recirculation from liver and muscle to adipose tissues. Thereafter the radioactivity decreased. When expressed per adipocyte uptake of label was not significantly different between white adipose tissues. The rate of decrease between 7 days and 4 months was, however, more rapid in mesenteric and inguinal than, particularly, epididymal, and, probably, retroperitoneal adipocytes. These results were partly parallel to in vitro data on lipoprotein lipase activity, which was not different between depots, and the rate of lipolysis, which was higher in mesenteric than other adipocytes. These results suggest that differences in weight increase of adipose tissue regions are due mainly to differences in the rate of mobilization of adipocyte triglycerides. When expressed per gram triglyceride, uptake and mobilization of label were clearly more rapid in mesenteric than other white adipose tissues. This is probably explained by a combination of a higher adipocyte density plus the metabolic characteristics of adipocytes in this depot. Since mesenteric adipose tissue is smaller than the other depots studied, the absolute contribution of this tissue to the energy supply of the body is probably not different from that of other adipose tissues, however. A large uptake and short half life was observed in interscapular adipose tissue. This region contains brown adipocytes, and the results therefore suggest that lipid uptake for thermogenic purposes is of a considerable magnitude. It was concluded that among white adipose tissues, the mesenteric tissue has a rapid turnover of triglyceride. This is probably due to a combination of a high density and specific metabolic characteristics of these adipocytes. Factors in the microenvironment of adipocytes probably contribute to the high turnover either directly, or by modification of cellular characteristics.     

Metabolism of isolated fat cells from various tissue sites in the rat: influence of hemorrhagic hypotension

The in vitro lipolytic response to norepinephrine by rat adipocytes from epididymal, subcutaneous, perirenal, mesenteric, and omental tissue sites was studied in control and hypotensive animals. Lipolysis per millimole of triglyceride was found to be three to four times higher in mesenteric and omental fat cells than in adipocytes of the other sites sampled. The high lipolytic activity of mesenteric and omental adipocytes was partly attributable to their smaller cell size; however, lipolysis per cell was also higher. Hemorrhagic hypotension caused a 50-60% decrease in lipolytic activity at four of the five sites studied. Adipocytes of omental origin maintained their lipolytic activity at the prehypotensive level, however, indicating that the metabolic adjustments brought about by hemorrhagic hypotension are not uniform at all adipose tissue sites.     

Lactate Production from Glucose and Response to Insulin in Perifused Adipocytes from Mesenteric and Epididymal Regions of Lean and Obese Rats

Lactate, an important metabolic substrate for peripheral tissues and the liver, is released in significant amounts from adipose tissue. Using a perifusion system, we measured lactate production from glucose and response to insulin in isolated mesenteric and epididymal adipocytes removed from fed or fasted male Wistar rats at two stages of growth and development: (a) lean rats (7 weeks to 9 weeks old, weighing ～250 g), and (b) fatter rats (6 months to 8 months old, weighing ～550 g). The results show that lactate production in perifused adipocytes is regulated by the prior nutritional state of the animals, by the adipose tissue region, and by the presence of insulin in the perifusate. In fat cells from lean rats, basal lactate production was significantly higher (p<0.05) in mesenteric cells when compared with epididymal cells, both in the fed state (7.8 nmol/10⁷ fat cells per minute vs. 2.9 nmol/10⁷ fat cells per minute) and after 2 days of fasting (13.6 nmol vs. 3.5 nmol). When the response to 1 mU/mL insulin was studied, however, the relative increase in lactate production produced by insulin was greater in the epididymal cells than in the mesenteric cells, in both the fed (194% vs. 91% over basal, respectively) and fasted (360% vs. 55% over basal, p<0.05) state. When larger epididymal adipocytes from fatter rats were compared with an equal number of smaller epididymal cells from leaner rats, the larger cells produced 4.99 nmol of lactate/10⁷ fat cells per minute, whereas the smaller cells produced 2.93 nmol (p=0.08). Large fat cells showed a small and nonsignificant response to insulin in either type of cell (epididymal vs. mesenteric) or nutritional state (fed vs. fasted). This study indicates that distinct regional differences exist in lactate production and response to insulin. Mesenteric adipose tissue, which drains directly into the portal vein and provides substrates to the liver, may be an important source of lactate for the hepatic processes of gluconeogenesis and glycogenesis.     

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.     

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.     

Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids

GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Gα_i. Here, we agree with a contradictory report in finding no expression of GPR41 in murine adipose tissue. Nevertheless, in the presence of adenosine deaminase to minimise Gα_i signalling via the adenosine A1 receptor, SCFA stimulated leptin secretion by adipocytes from wild-type but not GPR41 knockout mice. Expression of GPR43 was reduced in GPR41 knockout mice. Acetate but not butyrate stimulated leptin secretion in wild-type mesenteric adipocytes, consistent with mediation of the response by GPR43 rather than GPR41. Pertussis toxin prevented stimulation of leptin secretion by propionate in epididymal adipocytes, implicating Gα_i signalling mediated by GPR43 in SCFA-stimulated leptin secretion.     

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.     

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.     

Inflammatory Cytokine Gene Expression in Mesenteric Adipose Tissue during Acute Experimental Colitis

Background

Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

Methods

Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes.

Results

During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF.

Conclusions

Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.     

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.     

Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma

Factors which regulate expression of the haptoglobin (acute phase reactant) gene in adipocytes have been examined using 3T3-L1 cells. Haptoglobin expression was observed by Northern blotting in each of the major white adipose tissue depots of mice (epididymal, subcutaneous, mesenteric, and perirenal) and in interscapular brown fat. Expression occurred in mature adipocytes, but not in the stromal-vascular fraction. In 3T3-L1 cells, haptoglobin mRNA was detected from day 4 after the induction of differentiation into adipocytes. Lipopolysaccharide and the cytokines, TNFalpha and interleukin-6, resulted in substantial increases in haptoglobin mRNA in 3T3-L1 adipocytes; the increase (7-fold) was highest with TNFalpha. Increases in haptoglobin mRNA level were also induced by dexamethasone, noradrenaline, isoprenaline, and a beta3-adrenoceptor agonist. In contrast, haptoglobin mRNA was reduced by nicotinic acid and the PPARgamma agonist, rosiglitazone. RT-PCR showed that the haptoglobin gene was expressed in human adipose tissue (subcutaneous, omental). It is concluded that haptoglobin gene expression in adipocytes is stimulated by inflammatory cytokines, glucocorticoids, and the sympathetic system, while activation of the PPARgamma nuclear receptor is strongly inhibitory.     

Chronic ethanol and triglyceride turnover in white adipose tissue in rats: inhibition of the anti-lipolytic action of insulin after chronic ethanol contributes to increased triglyceride degradation

Chronic ethanol consumption disrupts whole-body lipid metabolism. Here we tested the hypothesis that regulation of triglyceride homeostasis in adipose tissue is vulnerable to long-term ethanol exposure. After chronic ethanol feeding, total body fat content as well as the quantity of epididymal adipose tissue of male Wistar rats was decreased compared with pair-fed controls. Integrated rates of in vivo triglyceride turnover in epididymal adipose tissue were measured using (2)H(2)O as a tracer. Triglyceride turnover in adipose tissue was increased due to a 2.3-fold increase in triglyceride degradation in ethanol-fed rats compared with pair-fed controls with no effect of ethanol on triglyceride synthesis. Because increased lipolysis accompanied by the release of free fatty acids into the circulation is associated with insulin resistance and liver injury, we focused on determining the mechanisms for increased lipolysis in adipose tissue after chronic ethanol feeding. Chronic ethanol feeding suppressed beta-adrenergic receptor-stimulated lipolysis in both in vivo and ex vivo assays; thus, enhanced triglyceride degradation during ethanol feeding was not due to increased beta-adrenergic-mediated lipolysis. Instead, chronic ethanol feeding markedly impaired insulin-mediated suppression of lipolysis in conscious rats during a hyperinsulinemic-euglycemic clamp as well as in adipocytes isolated from epididymal and subcutaneous adipose tissue. These data demonstrate for the first time that chronic ethanol feeding increased the rate of triglyceride degradation in adipose tissue. Furthermore, this enhanced rate of lipolysis was due to a suppression of the anti-lipolytic effects of insulin in adipocytes after chronic ethanol feeding.     

Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes

We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal adipose tissues. Expressions of inflammation related genes (IL-6, TNF-α, COX-2) were higher in the inguinal than the epididymal ATE. Similarly, expressions of marker genes of macrophage and monocyte (MPEG-1, CD68, F4/80, CD64) were higher in the stromal vascular fraction (SVF) isolated from inguinal ATE than that from epididymal ATE. However, expressions of lipolysis related genes (ATGL, HSL, perilipin-1) were higher in the epididymal adipocytes than inguinal adipocytes. Moreover, secretion of IL-6 and PGE(2) was higher from inguinal ATEs than from epididymal ATEs. There was a trend that the total levels of IL-6, TNF-α and PGE(2) in the media from inguinal ATEs co-cultured with primary rat hepatocytes were higher than that in the media from epididymal ATEs co-cultured with hepatocytes, although the significant difference was only seen in PGE(2). Lipolysis, measured as glycerol release, was similar in the ATEs isolated from inguinal and epididymal adipose tissues when cultured alone, but the glycerol release was higher in the ATEs isolated from epididymal than from inguinal adipose tissue when co-cultured with hepatocytes. Compared to epididymal ATEs, the ATEs from inguinal adipose tissue elicited a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs), particularly macrophages, in inguinal adipose tissue resulting in stronger responses in terms of hepatotoxicity and insulin-resistance.     

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.     

Observations on preadipocytes and their distribution patterns in rat adipose tissue

Microscopic examination of adipocytes isolated from adult rat epididymal adipose tissue revealed numerous small cells (< 10 μm) morphologically similar to larger adipocytes. These small adipocytes appear identical to a new classification of adipose cells termed preadipocytes. Electron micrographs of these preadipocytes revealed examples of cells < 10 μm in diameter in various stages of maturation and lipid accumulation. The percent distribution pattern of these small adipocytes was not significantly altered by exercise although exercise shifted the distribution patterns of the larger cells (> 30 μm) toward a smaller mean cell size. The quantitative significance of preadipocytes is not established but these preliminary observations indicate that adipocytes < 10 μm in diameter may account for a numerically greater proportion of the total adipocytes observed in collagenase isolated preparations than heretofore recognized, although their contribution to total adipose mass is probably negligible.     

Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells,and their interaction with dietary lipids

Existing theories of the origin of HIV-related adipose tissue redistribution syndrome cannot adequately explain simultaneous hypertrophy of certain depots and atrophy of others, or its occasional occurrence in untreated HIV infection. These experiments explore the hypothesis that hypertrophy of lymphoid tissue-containing adipose depots arises from drug-induced disruption to local interactions between perinodal adipocytes and activated lymphoid cells. Guinea pigs were fed on plain or lipid-supplemented (10% suet, sunflower or fish oil) chow ad libitum or restricted, and the popliteal lymph nodes were activated by repeated injection of lipopolysaccharide. Explants of perinodal and other samples from popliteal, mesentery, omentum and nodeless perirenal and epididymal depots were incubated with lymphoid cells and zidovudine, didanosine, lamivudine or stavudine at physiological concentrations (0.1-1 microg/ml) or interleukin-10 and interleukin-6, and basal and maximum lipolysis was measured. All drugs increased lipolysis from perinodal adipocytes, especially mesenteric, though less than exogenous cytokines. Effects on adipocytes from non-perinodal sites and nodeless depots were minimal. The sunflower-oil diet enhanced, and the fish-oil and restricted diets reduced, these effects. We conclude that these NRTI antiretroviral drugs modulate the local interactions between perinodal adipocytes and activated lymphoid cells. Local interactions, and hence the selective hypertrophy of node-containing adipose depots, may be curtailed by dietary manipulation.     

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.     

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.     

On the characteristics of mitochondrial monoamine oxidase in pancreas and adipose tissues from genetically obese mice.

The substrate specificity of mitochondrial monoamine oxidase (MAO) in pancreatic and adipose tissues of obese mice and their lean counterparts was determined. The pancreatic MAO of obese mice had a greater specific activity than that of the lean mice. The white adipose tissue MAO was found to be more active than the brown adipose MAO in both groups of mice. While there was no appreciable difference in the MAO activities of brown adipose tissues between obese and lean mice, the enzyme from the white adipose tissue of obese mice had a higher specific activity than that of the lean mice. The higher MAO activity in white adipose tissue was observed when tyramine or serotonin was employed as substrate but not with benzylamine. Examination of mitochondrial MAO from epididymal adipocytes revealed marked differences in the properties of the enzyme between whole adipose tissue and isolated adipocytes. The inhibition characteristics of MAO from these tissues were studied with the specific inhibitors clorgyline and deprenyl.