Effects of sucrose feeding and denervation on lipogenesis in brown adipose tissue

Rats were fed standard laboratory chow or sucrose + chow for 2-3 weeks. Sucrose feeding significantly increased the size and norepinephrine content of interscapular brown adipose tissue (BAT). Sucrose feeding stimulated in vivo lipogenesis in BAT, white adipose tissue, and liver. Unilateral denervation reduced BAT norepinephrine content by 90%, and significantly reduced BAT protein and DNA content. Prior surgical denervation of BAT had no effect on lipogenesis in chow-fed rats, but reduced the sucrose-induced lipogenesis in BAT by 75% and increased lipogenesis in retroperitoneal white adipose tissue of sucrose-fed rats. These data demonstrate that the optimal stimulation of lipogenesis in BAT by sucrose feeding requires innervation of this tissue.     

A role for insulin in the diet-induced thermogenesis of cafeteria-fed rats

Rats fed a varied and palatable “cafeteria” diet exhibited hyperphagia, increases in resting metabolic rate (VO₂) and the thermogenic response to noradrenaline as well as hypertrophy of brown adipose tissue (BAT). In streptozotocin-diabetic rats, cafeteria feeding failed to produce increases in VO₂ or the response to noradrenaline, although BAT mass was greater than in their respective stockfed controls. Replacement doses of insulin (protamine-zinc-insulin, PZI) at two levels (2 and 4 units/rat every alternate day) failed to restore the thermogenic response of diabetic rats to the cafeteria diet. Acute replacement (8 units PZI) 12hr before the measurements resulted in resting and noradrenaline-stimulated values for VO₂ that were similar to those of non-diabetic cafeteria rats. These findings suggest an insulin requirement for diet-induced thermogenesis and the failure of diabetic rats to maintain body temperature when exposed to cold (5°C) suggests a further insulin requirement for cold-induced thermogenesis. In non-diabetic cafeteria rats, plasma insulin levels were significantly lower than those of stock fed controls in spite of a high carbohydrate intake and normal blood glucose.     

Dietary sodium restriction exacerbates age-related changes in rat adipose tissue and liver lipogenesis

To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.     

Effects of age on diet-induced thermogenesis and brown adipose tissue metabolism in the rat

Measurements of energy balance, thermogenic responses to noradrenaline and brown adipose tissue (BAT) activity were performed in male Lister-hooded rats aged 3.5 and 6.5 months, and fed either a pelleted control diet or a palatable cafeteria diet for 15 d. Cafeteria feeding produced increases in energy intake of 34 and 30 per cent in 3.5 and 6.5-month-old rats respectively, and energy expenditure was elevated by 25 and 10 per cent in these groups. Three-and-a-half-month-old cafeteria-fed rats gained more energy than their controls, but net energetic efficiency was significantly reduced, while in the older cafeteria rats, body energy gain was markedly increased without any apparent effect on net efficiency. The thermogenic response to noradrenaline was enhanced by cafeteria feeding at both ages. The younger cafeteria-fed rats showed significant increases in the mass, protein content and mitochondrial yield of BAT, and the activity of the mitochondrial proton conductance pathway, assessed from GDP-binding, was greater than their controls. The 6.5-month-old cafeteria group also showed hypertrophy of BAT and small, but not significant, increases in the protein content of the tissue and mitochondrial GDP-binding. These results demonstrate that rats aged 3.5 months can exhibit diet-induced thermogenesis and activate BAT in response to overfeeding, but the capacity for thermogenesis declines with age and was virtually absent in 6.5-month-old rats.     

Lipoprotein lipase of adipose tissue and skeletal muscle in human obesity: Response to glucose and to semistarvation

Obesity is frequently associated with elevated plasma levels of triglyceride and very low density lipoproteins (VLDL). It is possible that this could be at least partly attributed to defective removal of triglycerides from circulation. Therefore, we studied the response of tissue lipoprotein lipase (LPL) activity to stimulation by glucose and to suppression by caloric deficiency in subjects with simple obesity and in nonobese controls. A five-hour intravenous infusion of glucose increased the LPL activity in both adipose tissue and skeletal muscle. The average rise was 2.5-fold in nonobese subjects but only 1.8-fold in obese patients (p < 0.05). The decrease of response was similar in obese subjects with and in those without hypertriglyceridemia suggesting that the change was due to obesity as such. During feeding a 400 cal diet for 7 days the LPL activity of obese subjects fell by an average of 50% in adipose tissue and by 40% in skeletal muscle. The decreases are smaller than previously found in nonobese human subjects in a similar experiment. The magnitude of decrease of LPL activity in both tissues was positively correlated with initial enzyme activity but was not influenced by serum triglyceride level. During starvation the HDL cholesterol levels were reduced the change being positively related to simultaneous decreases of LPL activity in adipose tissue and in skeletal muscle. It is concluded that the metabolic regulation of tissue LPL activity (of the heparin-releasable pool) is abnormal in obesity. This may be related to insulin resistance of obese people and it may explain why obese people are basically more prone to develop hypertriglyceridemia than lean ones. The resistance of LPL to caloric restriction in obese subjects could bear on difficulties in reducing the adipose tissue mass.     

Hepatic triglyceride lipase is not an insulin-dependent enzyme in rats

The aim of this study is to examine whether insulin regulates the activity of hepatic triglyceride lipase. The activities of both hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL) were measured in plasma after intravenous administration of heparin. Insulin-deficient diabetic rats had normal H-TGL activity. Insulin-treated normal rats had no different enzyme activities from those of controls. Ventromedial hypothalamic (VMH) lesioned rats that became obese and showed hyperinsulinemia, had also normal enzyme activities. From these experiments, it is concluded that H-TGL is not an insulin-dependent enzyme. As far as LPL is concerned, this enzyme was increased in both insulin-treated rats and rats with VMH lesions. This was consistent with the established fact that insulin has a stimulatory effect on adipose tissue LPL. The LPL activity in postheparin plasma was not decreased in insulin-deficient rats. It is speculated that a possible increase in muscle LPL compensated for the low adipose tissue LPL in diabetic rats.     

Cafeteria feeding promotes diet-induced thermogenesis in monosodium glutamate-treated mice

We studied diet-induced thermogenesis (DIT) in cafeteria fed monosodium glutamate (MSG) and saline-treated mice. From 12 weeks of age MSG and saline-treated mice were fed a diet of either standard chow or a cafeteria diet of standard chow supplemented with chocolate or biscuits on alternate days for six weeks. There was a significant weight gain in cafeteria fed MSG-treated mice but not in cafeteria fed saline-treated mice. In cafeteria fed MSG-treated mice there was a significant increase in resting oxygen consumption. The response to exogenous norepinephrine was significantly increased in cafeteria fed saline-treated mice. The level of specific tritiated guanosine 5'-diphosphate binding to isolated mitochondrial fractions was significantly increased in both cafeteria fed MSG and saline-treated mice. It is concluded that (1) cafeteria feeding is capable of promoting DIT, within brown adipose tissue (BAT), in MSG-treated mice and (2) the mechanisms for the induction of thermoregulatory thermogenesis (TRT) and DIT are distinct since cold-induced TRT has previously been shown to be defective in MSG-treated mice.     

Pinealectomy Has No Effect on Diet-Induced Thermogenesis and Brown Adipose Tissue Proliferation in Rats

The role of the pineal gland in diet-induced thermogenesis (DIT) and growth of brown adipose tissue (BAT) in rats during voluntary overfeeding was studied using pinealectomized and sham-pinealectomized rats. Overfeeding was induced by offering the animals a cafeteria-diet (CD) which contained a selection of highly palatable food items. Rats which were fed CD had significantly increased interscapular brown adipose tissue (IBAT) mass and increased tail-skin temperature indicating the importance of the tail in thermoregulation during DIT. Pinealectomy had no effect on the increase in tail-skin temperature and deposition of IBAT, which were stimulated by CD feeding. These findings suggest that the pineal is not directly involved in modulating the metabolism of BAT in rats.     

Contribution of hyperinsulinemia to modulation of lipoprotein lipase activity in the obese Zucker rat

This study was designed to assess the contribution of hyperinsulinemia to the maintenance of high adipose and low muscle lipoprotein lipase (LPL) activity in the obese Zucker fa/fa rat. Insulinemia in obese Zucker rats was reduced for 4 days with a single injection of low-dose streptozotocin (STZ). Saline-injected intact obese (obese-INT) and STZ-injected obese (obese-STZ) rats were compared with a lean Fa/? reference group. LPL activity was assessed after a 12-hour fast, with or without a 1-hour refeeding period. Fasting serum insulin levels were 17-fold higher in obese-INT versus lean rats and were reduced to 60% of obese-INT levels in obese-STZ animals. In the postprandial state, serum insulin levels remained low in obese-STZ rats and were similar to the values in lean animals, whereas insulinemia increased in the obese-INT group to 18-fold the levels in lean rats. Serum glucose, nonesterified fatty acid (NEFA), and triglyceride levels, which were higher in obese-INT versus lean rats, were further increased in the obese-STZ group. Tissue weights of obese rats were unaffected by STZ treatment. Fasting LPL specific activity was higher in white adipose tissue ([WAT] +87%) and brown adipose tissue ([BAT] +167%) of obese-INT versus lean rats. Reducing the insulinemia in obese-STZ rats reduced fasting enzyme activity to the levels in lean animals in both WAT and BAT. Insulinemia and adipose LPL activity were positively correlated in the fasted state. Acute food intake increased WAT LPL activity in lean animals, but not in obese animals. Soleus LPL activity was lower in obese-INT compared with lean rats and was further decreased in obese-STZ animals. Heart LPL was decreased only in obese-STZ rats compared with the lean group. LPL in muscle tissue was not correlated with insulinemia, but an inverse relationship was found between serum NEFA levels and enzyme activity. It is concluded that in the obese Zucker rat, hyperinsulinemia is responsible for the maintenance of elevated basal LPL activity in adipose tissue independently of fat mass, whereas muscle enzyme activity appears to be more strongly and inversely related to the availability or tissue utilization of lipid substrates.     

Influence of alcohol and sucrose consumption on energy balance and brown fat activity in the rat

Voluntary intake of solutions of alcohol (7%) and sucrose (10%) represented 20% and 25% of total metabolizable energy intake, respectively, in young male rats maintained on a stock diet, but total energy intake was similar to that of controls drinking water. Body weight and energy gains were similar for control and sucrose-treated rats but were significantly reduced in the group drinking alcohol, and energy expenditure, corrected for body size (kJ/kg0.75/day), was elevated in rats drinking alcohol (17% above control) or sucrose (18%). Gross and net energetic efficiencies were markedly depressed by consumption of alcohol but not by consumption of sucrose. Resting oxygen consumption, before and after injection of norepinephrine (25 micrograms/100 g body weight) was similar for all groups. Brown adipose tissue (BAT) mass and mitochondrial protein did not differ between groups, but the activity of the mitochondrial proton conductance pathway, assessed from the binding of 3H-guanosine diphosphate, was significantly elevated by alcohol and sucrose consumption. Thus, the increased energy expenditure associated with alcohol and sucrose ingestion may involve BAT thermogenesis, but this alone cannot explain the larger effects of alcohol on metabolic efficiency.     

Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity

Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT.     

Mice lacking the thyroid hormone receptor-alpha gene spend more energy in thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced obesity

Unable to activate brown adipose tissue (BAT) thermogenesis, alphaT3-receptor-deficient mice (Thra-0/0) are cold intolerant. Our objective was to investigate the impact on energy economy and mechanisms of the alternate facultative thermogenesis developed. Energy expenditure (oxygen and food consumption) is elevated in Thra-0/0 mice reared at room temperature. Such difference disappears at thermoneutrality (30 C) and expands as ambient temperature becomes colder (P < 0.001). Despite eating more, Thra-0/0 are leaner than wild-type (WT) mice (P < 0.01), whereas these, whether on chow or high-fat diet, gained more weight (g/d: 0.12 +/- 0.002 vs. 0.08 +/- 0.002 and 0.25 +/- 0.005 vs. 0.17 +/- 0.005, respectively) and adiposity than Thra-0/0 mice (P < 0.001). The respiratory quotient was lower in Thra-0/0 than WT mice (P < 0.001), after feeding or fasted, on chow or high-fat diet, indicating a preference for fat as fuel, which was associated with increased lipoprotein lipase (LPL) expression in skeletal muscle of Thra-0/0 mice but with no differences in gene expression in white adipose tissue. Type-2 deiodinase (D2) was increased in BAT and aerobic muscle of Thra-0/0 mice. This and liver D1 were increased by a high-fat diet in both genotypes, as also were serum T3 and T3/T4 ratio, but more in Thra-0/0 than WT mice (P < 0.001). Remarkably, when studied at thermoneutrality, genotype differences in weight and adiposity gain, respiratory quotient, D2, and LPL disappeared. Thus, disruption of BAT thermogenesis in Thra-0/0 mice activates an alternate facultative thermogenesis that is more energy demanding and associated with reduced fuel efficiency, leanness, increased capacity to oxidize fat, and relative resistance to diet-induced obesity, in all of which muscle LPL and deiodinases play a key role.     

Recent advances in adaptive thermogenesis: potential implications for the treatment of obesity

Large inter-individual differences in cold-induced (non-shivering) and diet-induced adaptive thermogenesis exist in animals and humans. These differences in energy expenditure can have a large impact on long-term energy balance and thus body weight (when other factors remain stable). Therefore, the level of adaptive thermogenesis might relate to the susceptibility to obesity; efforts to increase adaptive thermogenesis might be used to treat obesity. In small mammals, the main process involved is mitochondrial uncoupling in brown adipose tissue (BAT), which is regulated by the sympathetic nervous system. For a long time, it was assumed that mitochondrial uncoupling is not a major physiological contributor to adaptive thermogenesis in adult humans. However, several studies conducted in recent years suggest that mitochondrial uncoupling in BAT and skeletal muscle tissue in adult humans can be physiologically significant. Other mechanisms besides mitochondrial uncoupling that might be involved are futile calcium cycling, protein turnover and substrate cycling. In conjunction with recent advances on signal transduction studies, this knowledge makes manipulation of adaptive thermogenesis a more realistic option and thus a pharmacologically interesting target to treat obesity.     

The influence of the sympathetic nervous system on brown adipose tissue: an experimental and histopathologic study on aging]

Brown adipose tissue (BAT) is known to be a principal energy source of non-shivering thermogenesis and related diet-induced thermogenesis. These regulate body temperature and body weight and are controlled by the dissipation of excessive dietary caloric intake. We carried out histopathologic, immunohistochemical and biochemical studies of BAT in rats in relation to aging changes. Four groups of Donryu strain male rats (5 each of 1 month, 2 months, 4 months and 20 months of age) were used. They had been given commercial chow and tap water ad libitum and were kept in an air-conditioned room. Body weight (BW), interscapular BAT weight (IBATW) and g IBATW/g BW of rats were measured. Nor-adrenalin (NA), and dopamine-beta-hydroxylase (DBH) of IBAT were determined. To evaluate the catecholaminergic effects of BAT, morphometric quantitation of BAT was carried out based on the cytoplasmic locularity of fat globules in the BAT cells. Distribution of DBH in BAT was assessed immunohistochemically by the avidin biotin peroxidase complex method. With the use of statistical analysis of variance procedure, there were highly significant decreases in the ratio of g IBATW/g BW (p less than 0.0001) and in the concentrations of NA (p less than 0.0001) and DBH (p less than 0.01) between young (weaning at 1 month old) rats and adult (aged from 4 to 20 months) rats. In the morphometric measurement, by the statistical analysis system (SAS) Spearman correlation coefficient method, there was a significant increase of Type 5 cell (monocular brown adipose tissue cell) in 4 month and 20 month rats, compared to 1 month and 2 month rats (p less than 0.05). Immunohistochemical study of BAT showed localization of DBH in perivascular mesenchymal cells which corresponded with the morphologic distribution of catecholamine as reported by Lever. The results suggest that in the processes of aging in the rat there are reductions in the ratio of g IBATW/g BW, NA and the activity in DBH.     

Lipoprotein lipase activity and cellularity in brown and white adipose tissue in Zucker obese rats

The genetically obese adult Zucker rat (fafa) exhibits reduced thermogenesis when stimulated by physiological agents (cold, catecholamines). Recent evidence suggests that this thermogenic defect may be important in the manifestation of the animal's obesity and that it reflects a reduced thermogenic contribution from brown adipose tissue, the major nonshivering thermogenic site in many mammals. The present study describes the effects of the obese genotype on brown (and white) adipocyte size, number, and lipid content and tissue lipoprotein lipase (LPL) activity. In the obese rats, brown fat depots were increased in mass. This increase could be accounted for by brown fat hypertrophy (due primarily to an increase in the amount of triglyceride present in each cell) rather than hyperplasia (there being no increase in the number of brown fat cells). In addition, unlike the situation in white fat, the brown fat from the obese rats did not exhibit higher LPL activity than did the brown fat from their lean littermates. This absence of an increased capacity for triglyceride uptake, coupled with the greater amount of triglyceride per brown adipocyte, is consistent with a reduction of triglyceride oxidation (and, thus, heat production) in the cells from the obese (v the lean) rats.     

Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression

The effects of the chronic activation of the central melanocortin (MC) system by melanotan II (MTII) were assessed in chow-fed (CH) and high-fat (HF) diet-induced obese (DIO) Sprague-Dawley rats. Six-day central infusion of MTII (1 nmol/day) reduced body weight and visceral adiposity compared with ad libitum-fed control and pair-fed groups and markedly suppressed caloric intake in both CH and DIO rats. The anorexic response to MTII was similar in DIO relative to CH rats. MTII induced a sustained increase in oxygen consumption in DIO but a delayed response in CH rats. In both diet groups, MTII reduced serum insulin and cholesterol levels compared with controls. HF feeding increased brown adipose tissue (BAT) uncoupling protein 1 (UCP1) by over twofold, and UCP1 levels were further elevated in MTII-treated CH and DIO rats. MTII lowered acetyl-CoA carboxylase expression and prevented the reduction in muscle-type carnitine palmitoyltransferase I mRNA by pair-feeding in the muscle of DIO rats. Compared with CH controls, hypothalamic MC3 and MC4 receptor expression levels were reduced in DIO controls. This study has demonstrated that, despite reduced hypothalamic MC3/MC4 receptor expression, anorexic and thermogenic responses to MTII are unabated with an initial augmentation of energy expenditure in DIO versus CH rats. The HF-induced up-regulation of UCP1 in BAT may contribute to the immediate increase in MTII-stimulated thermogenesis in DIO rats. MTII also increased fat catabolism in the muscle of DIO rats and improved glucose and cholesterol metabolism in both groups.     

Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue

The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R-/- and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R-/- mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.     

Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat.

In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.     

Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans)

Only with the development of the uncoupling protein 1 (UCP1)-ablated mouse has it become possible to strictly delineate the physiological significance of the thermogenic capacity of brown adipose tissue. Considering the presence of active brown adipose tissue in adult humans, these insights may have direct human implications. In addition to classical nonshivering thermogenesis, all adaptive adrenergic thermogeneses, including diet-induced thermogenesis, is fully dependent on brown adipocyte activity. Any weight-reducing effect of β(3)-adrenergic agonists is fully dependent on UCP1 activity, as is any weight-reducing effect of leptin (in excess of its effect on reduction of food intake). Consequently, in the absence of the thermogenic activity of brown adipose tissue, obesity develops spontaneously. The ability of brown adipose tissue to contribute to glucose disposal is also mainly related to thermogenic activity. However, basal metabolic rate, cold-induced thermogenesis, acute cold tolerance, fevers, nonadaptive adrenergic thermogenesis and processes such as angiogenesis in brown adipose tissue itself are not dependent on UCP1 activity. Whereas it is likely that these conclusions are also qualitatively valid for adult humans, the quantitative significance of brown adipose tissue for human metabolism--and the metabolic consequences for a single individual possessing more or less brown adipose tissue--awaits clarification.     

Metabolic studies of adipose tissue in acute uremia

The effect of acute uremia on lipoprotein lipase (LPL) activity in rat adipose tissue and on the response of the isolated adipocytes to insulin was assessed. LPL activity in adipose tissue and in adipocytes of the uremic rats was decreased compared with values in sham-operated controls. Also, the adipocytes from uremic rats released significantly less than control amounts of LPL. In contrast, glucose oxidation by adipocytes isolated from uremic rats was not different from controls, and there was no difference in insulin binding or in insulin-stimulated glucose oxidation in the two groups. Triglyceride injected into the uremic rats was cleared at about half the control rate. Thus, the specific reduction in LPL activity in adipose tissue may be responsible, at least in part, for the defective removal of triglyceride. However, it is unlikely that the reduced LPL is due to a generalized toxic effect of uremia on adipose tissue since no significant alteration in insulin binding and glucose oxidation was found.