Effect of cold acclimation on brown adipose tissue fatty acid synthesis in rats adapted to a high-protein, carbohydrate-free diet

The effect of cold acclimation on brown adipose tissue (BAT) fatty acid synthesis was investigated in rats adapted to a high-protein, carbohydrate-free diet. At an ambient temperature (25 degrees C), rates of fatty acid synthesis in BAT from rats adapted to the high-protein diet were reduced to 27% of rats fed the balanced diet and increased markedly after cold acclimation (10 days at 4 degrees C), although the increase was smaller than in control rats. BAT weight increase induced by cold acclimation was smaller in rats fed the high-protein diet (30%) than in controls (100%). When expressed per whole tissue, maximal activities of BAT glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate (ATP)-citrate lyase, and acetyl-coenzyme A carboxylase were markedly reduced in high-protein diet-adapted rats at 25 degrees C and increased after cold acclimation in BAT from the 2 groups. However, when expressed per milligram protein, only acetyl-coenzyme A carboxylase showed an increase in both controls and in rats fed the high-protein diet. G6P-dehydrogenase, malic enzyme, and ATP-citrate lyase increased (per milligram protein) only in rats adapted to the high-protein diet and actually decreased in BAT from cold-acclimated control rats. Initial (before activation) pyruvate dehydrogenase (PDH) complex activity was lower in BAT from rats fed the high-protein diet at 25 degrees C and increased in cold-acclimated rats from the 2 groups. Circulating levels of insulin decreased in the 2 groups after cold acclimation. The data suggest that the cold acclimation-induced increase in BAT lipogenesis in rats adapted to the high-protein diet was due to a restoration of sympathetic activity, which induced both BAT hyperplasia and activation of adipocyte free fatty acid (FFA) synthesis, with an important participation of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase.     

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.     

Relative importance of sympathetic outflow and insulin in the reactivation of brown adipose tissue lipogenesis in rats adapted to a high-protein diet

The effect of denervation or acute insulin deficiency on brown adipose tissue lipogenesis was investigated in rats adapted to a high-protein diet before and after diet reversion to a balanced diet. Denervation of rats fed the balanced diet induced a 50% reduction in in vivo rates of brown adipose tissue fatty acid synthesis, with decreased activities of acetyl-CoA carboxylase and adenosine triphosphate (ATP)-citrate lyase. The markedly (80%) reduced fatty acid synthesis and enzyme activities in brown adipose tissue from rats adapted to the high-protein diet were not affected by denervation. Replacement of the high-protein diet by the balanced diet for 24 hours restored fatty acid synthesis to normal levels, but recovery of enzyme activities was only partial. Lipogenesis restoration and partial recovery of enzyme activities were impaired in denervated tissue from high-protein diet-fed rats. In all experimental conditions, the activities of acetyl-CoA carboxylase and ATP-citrate lyase showed a better correlation with brown adipose tissue lipogenesis than the generators of H(+), glucose-6-P dehydrogenase, and malic enzyme. Anti-insulin serum administration during the 12- to 24-hour period after diet reversion completely blocked lipogenesis recovery in innervated and denervated tissues and drastically reduced brown adipose tissue lipogenesis of concomitantly injected rats fed the balanced diet. The data suggest that efficient and rapid adjustments of brown adipose tissue lipogenesis require sympathetic activation, and that this tissue can maintain significant, albeit reduced, rates of lipogenesis in the absence of sympathetic activation, but not in the absence of insulin.     

Brown adipose tissue metabolism in hypothalamic-obese rats

Studies were performed to evaluate the metabolic changes of brown adipose tissue (BAT) in rats with hypothalamic obesity (VMNL). In vitro 14C-palmitate oxidation and incorporation into triglycerides were similar in VMNL and control rats. However, protein and fatty acid content and incorporation of 14C-palmitate into phospholipid were significantly less in both hyperphagic and normophagic VMNL rats. In order to assess in vivo BAT lipogenesis, rats were injected with 3H2O. Plasma H2O incorporation into BAT lipids was significantly greater in VMNL rats. Likewise, BAT lipid content was higher in obese rats. In another experiment BAT was incubated with U-14C-glucose to evaluate glucose utilization by BAT. 14C-glucose was oxidized and incorporated into both lipids and glycogen more rapidly by obese than by normal rat BAT. Glycogen content was greater in VMNL rats. Tissues were also incubated with 1-14C-pyruvate and 2-14C pyruvate. Pyruvate incorporation into glyceride glycerol and oxidation of 2-14C pyruvate through the Krebs cycle were similar in both obese and control rats. However, the incorporation of pyruvate into glyceride fatty acids was increased in VMNL rats. The results indicate that both fatty acid and lipid synthesis are increased in BAT of obese rats whereas lactate production is decreased and Krebs cycle activity is normal. Some of these changes appear to be independent of the level of food intake.     

Comparative study of the lipogenic potential of human and rat adipose tissue

The reported low activity of lipogenic enzymes (especially adenosine triphosphate [ATP]-citrate lyase) in human adipose tissue led to the general conclusion that in humans lipogenesis occurs primarily in the liver. However, recent studies indicate that the liver plays a minor role in de novo lipogenesis and suggest that adipose tissue may be the principal lipogenic human tissue. In an attempt to resolve these contradictions we reinvestigated the lipogenic potential of human adipose tissue and compared with adipose tissue of rats fed a high-fat diet for 2 weeks and fasted overnight before death. These conditions mimic the nutritional state of patients at the moment of tissue sampling. We found that overnight fasting of the rats maintained previously for 12 days on a high-fat diet caused a decrease of ATP-citrate lyase of about 7-fold. Thus, in human adipose tissue, the mean activity of ATP-citrate lyase was approximately 8 times lower than in rats fed a high-fat diet and fasted overnight, and about 50 times lower than in rats maintained on normal laboratory diet. Unlike ATP-citrate lyase, fatty acid synthase (FAS) activity was only slightly lower in human adipose tissue than in rats maintained on a normal laboratory diet. Comparable FAS activity was found when rats were fed a high-fat diet and fasted overnight. The average activities of human adipose tissue acetyl-coenzyme A carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase were approximately 3-, 4-, and 6-fold lower than in adipose tissue from rats fed a high-fat diet and fasted overnight before tissue sampling, while the activity of 6-phosphogluconate dehydrogenase in humans was higher than in rat adipose tissue. No significant differences in lipogenic enzyme activities were found between male and female and between lean and obese patients. The rate of fatty acid synthesis in intact pieces of human adipose tissue was approximately 5 times lower than in adipose tissue pieces of rats fed a high-fat diet and fasted overnight before tissue samples were taken. The comparison of the lipogenic potential of humans and rats (maintained on the diet to mimic the nutritional state of patients at the time of tissue sampling) suggests that human adipose tissue is an important site of fatty acid synthesis.     

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.     

Effect of sucrose overfeeding on brown adipose tissue lipogenesis and lipoprotein lipase activity in rats

During cold-induced nonshivering thermogenesis, interscapular brown adipose tissue (BAT) lipoprotein lipase (LPL) activity and lipogenesis are elevated. Because of the many similarities between cold- and diet-induced thermogenesis, we examined the effect of ad libitum access to a 32% sucrose solution on caloric intake, adiposity, and BAT enzyme activities in male rats. Daily caloric intakes of sucrose-fed animals were elevated by 20%-25%, and 8 wk of sucrose feeding doubled carcass fat content. This sucrose-feeding induced obesity was associated with increases in circulating triglyceride and insulin levels as well as increased retroperitoneal white adipose tissue LPL activity. However, the increased carcass lipid content accounted for less than half of the excess calories ingested by the sucrose-fed rats. Sucrose feeding stimulated in vivo lipogenesis in BAT and elevated BAT fatty acid synthetase and acetyl-CoA carboxylase activities but not LPL activity. These findings suggest that overeating enhances endogenous lipogenesis but not uptake of circulating triglyceride in BAT. Thus, both cold- and diet-induced thermogenesis increase BAT lipogenesis, while only cold-induced thermogenesis is associated with elevated LPL activity in BAT.     

Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat

To study the use of glucose for lipid synthesis by the periuterine adipose tissue in situ, 14C-glucose was infused through the left uterine artery of anesthetized, fed pregnant and virgin control rats. A greater amount of 14C-lipid always appeared in the adipose tissue from the left uterine horn than in the tissue from the right uterine horn, indicating direct utilization of the infused 14C-glucose by the tissue. Glucose utilization for both glycerol and fatty acid synthesis increased from day 0 (virgin rats) to day 20 of gestation and then decreased dramatically on day 21. In virgin and 12-day pregnant rats, glucose was incorporated into either lipidic moiety at similar rates, whereas in late pregnant rats glucose utilization for glyceride glycerol synthesis was four to five times greater than for fatty acids. The utilization of circulating fatty acids and the lipoprotein triglyceride-derived fatty acids was studied by infusing 14C-palmitate or 14C-triolein-labeled very-low-density lipoprotein (VLDL) through the left uterine artery in both virgin and 20-day pregnant rats. Incorporation of fatty acids from either one of these plasma sources was significantly higher in the pregnant than in virgin rats. This high amount of fatty acid acquisition did not account for the very active glyceride glycerol synthesis observed in pregnant rats and can only be explained by the intracellular reesterification of some lipolytic fatty acids. The results suggest a highly accelerated triacylglycerol/fatty acid substrate cycle in adipose tissue during late pregnancy, which would allow active esterification (contributing to fat accumulation) and responsive lipolysis (permitting rapid fat mobilization) by the mother.     

Fatty acid synthesis by human adipose tissue

The effect of age and nutritional status on the synthesis of fatty acids from a variety of labeled substrates by human adipose tissue in vitro was investigated. The results of this study clearly demonstrate that, although human adipose tissue is able to oxidize glucose to CO₂, its ability to incorporate glucose-carbon into long chain fatty acids is negligible. Although the utilization of acetate for the synthesis of fatty acids by adipose tissue is substantial in the presence of glucose and insulin, its physiologic significance in human under normal dietary conditions is questionable. That the capacity of human adipose tissue is limited is further supported by (1) a negligible incorporation of pyruvate-3-¹⁴C (up to 25 mM concentration in the incubation medium) into fatty acids, (2) a lack of stimulation in lipogenesis by human adipose tissue after refeeding a diet high in carbohydrate and very low in fat to a previously starved human, and (3) an extremely low activity of pyruvate carboxylase and ATP-citrate lyase in adipose tissues from humans of varying ages. The activities of other key lipogenic enzymes, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malate dehydrogenase, are also low. These enzymes can be stimulated in human adipose tissue after a fasting-refeeding regimen. The activity of phosphoenolpyruvate carboxykinase is also very low in human adipose tissue, and it is suggested that a pathway of glyceroneogenesis may not play a significant role in human adipose tissue. In light of our results, together with previous reports, it is possible to conclude that the capacity of human adipose tissue to utilize a dietary carbohydrate for the synthesis of fatty acids is extremely low and that the liver plays a major role in the biosynthesis of endogenous fatty acids from dietary carbohydrate in the human.     

Thermogenesis and brown adipose tissue activity in high fat fed Osborne-Mendel rats

The consequences of hyperlipidic feeding on interscapular brown adipose tissue (IBAT) activity were examined in the cold-acclimated rat. Male Osborne-Mendel rats (7 weeks old) were exposed for 10 weeks at either 28 or 5 degrees C. The rats were fed a semipurified diet (normal fat (NL): 5% lard; high fat (HL): 54% lard) for the last 9 weeks. IBAT weight was greater in HL than in NL rats. This increase was entirely due to accumulation of neutral lipids. Among different IBAT components (proteins, DNA, phospholipids) no variations were observed in HL 28 degrees C rats. HL diet did not modify lipoprotein lipase and cytochrome oxidase activities, but an increase in purine nucleotide binding (taken as an index of thermogenic activity) was observed in HL 28 degrees C rats. Cold acclimation led to comparable stimulation in NL and HL rats. The calorigenic effect of norepinephrine in vivo was not modified by HL diet. Study of arteriovenous differences showed that IBAT fatty acid and glycerol release by norepinephrine was slightly increased in HL 28 degrees C rats. No effect of HL diet was observed at 5 degrees C. These results indicate that HL feeding leads to a moderate increase in the IBAT thermogenic capacity of Osborne-Mendel rats. HL diet does not modify the normal development of nonshivering thermogenesis when rats are kept in a cold environment.     

De novo lipogenesis in adipose tissue of lean and obese women: application of deuterated water and isotope ratio mass spectrometry

OBJECTIVE: To evaluate the feasibility of using deuterated water and isotope ratio mass spectrometry to measure de novo fatty acid synthesis in adipose tissue, and to compare this parameter in obese and lean women. SUBJECTS: Six lean and six obese premenopausal Caucasian women in the main study and three obese Pima Indians in a pilot study. MEASUREMENTS: Deuterated water was administered orally twice daily for 14 days to create stable deuterium enrichment in body water, during which series of blood samples were collected to measure body water deuterium enrichment and deuterium incorporation into plasma total Triacylglycerol (TG) fatty acids and total cholesterol. Subcutaneous fat at different sites were sampled at the beginning and the end of deuterium administration to measure deuterium incorporation into TG fatty acids. RESULTS: Fractional de novo synthesis rate of TG fatty acids in adipose tissue was 0. 014+/-0.005 and 0.014+/-0.007% in lean and obese Caucasian women, corresponding to 2+/-0.7 and 5.6+/-3.2 g (P=0.3) of fatty acids synthesized daily, respectively. Plasma TG fatty acids and cholesterol synthesis rates were comparable to those reported previously. A pilot study showed that de novo lipid synthesis in adipose tissue of obese Pima Indians was also quantitatively minor. CONCLUSION: Human adipose tissue, like the liver, does not make a major contribution to whole body lipogenesis under eucaloric conditions. A combination of deuterated water and isotope ratio mass spectrometry is a useful research tool for studying accumulation of de novo synthesized lipids in human adipose tissue.     

Increased glyceroneogenesis in adipose tissue from rats adapted to a high-protein, carbohydrate-free diet: role of dietary fatty acids

We have previously shown in in vivo experiments that adipose tissue glyceroneogenesis is increased in rats adapted to a high-protein, carbohydrate-free (HP) diet. The objectives of the present study were (1) to verify if the increased glyceroneogenic activity is also observed in isolated adipocytes and (2) to investigate the role of preformed fatty acids in the production of the increased adipose tissue glyceroneogenesis. Control rats received a balanced diet, with the same lipid content of the HP diet. Glyceroneogenic activity was found to be higher in adipocytes from HP rats than in controls, as evidenced by increased rates of conversion of pyruvate and lactate to triacylglycerol (TAG)-glycerol. Administration of Triton WR 1339, which blocks the removal of TAG incorporated into circulating lipoproteins, to HP diet-adapted rats caused a significant reduction in the incorporation of 14C-pyruvate into TAG-glycerol by adipose tissue, which was accompanied by a marked inhibition of phosphoenolpyruvate carboxykinase activity, the key enzyme of glyceroneogenesis. The inhibitory effect of Triton on TAG-glycerol synthesis by adipose tissue was also observed in vivo, after administration of 3H2O. Adaptation to the HP diet induced a marked increase in the activity of retroperitoneal and epididymal fat LPL, which was restored to control values 24 hours after replacement of the HP diet by the balanced diet. The data suggest that in rats adapted to a carbohydrate-free diet, adipose tissue glyceroneogenesis is activated by an increased use of diet-derived fatty acids.     

Lipogenesis in situ in the genetically obese Zucker fatty rat (fa/fa): Role of hyperphagia and hyperinsulinaemia

Summary In situ fatty acid synthesis has been measured with ³H₂O in anaesthetised lean and obese Zucker (fa/fa) rats. The accumulation of fatty acids was increased in both the liver and adipose tissue of young fa/fa rats as a result of both an increased rate of lipogenesis and an increase in tissue mass. Whereas total hepatic lipogenesis increased with age, total adipose tissue lipogenesis decreased in older fa/fa rats. Experiments with hepatectomized rats showed that the liver was the major site of the excess fatty acid synthesis in fa/fa rats. The enhanced rate of lipogenesis in fa/fa rats was abolished by either pairfeeding or streptozotocin treatment. The results suggest that the increased fatty acid synthesis in fa/fa rats is secondary to the hyperphagia, hpyerinsulinaemia, and increased mass of hepatic and adipose tissues.The authors are grateful to the M. R. C. for award of a project grant.     

Tissue-specific regulation of fatty acid synthesis by thyroid hormone.

It is generally agreed that thyroid hormone stimulates the hepatic synthesis of long chain fatty acids in the rat. However, there are conflicting data about its effects in white adipose tissue, while in brown adipose tissue, lipogenic rates are highest in hypothyroid animals. We have systematically examined the effect of thyroid state on lipogenesis in different rat tissues. Fatty acid synthesis was assessed in vivo, using the incorporation of tritiated water. Hepatic lipogenesis was induced 16-fold between hypothyroid (4.1 +/- 0.6 microns H incorporated/g.h) and hyperthyroid rats (66.5 +/- 13.2 microns H/g.h). Kidney and heart were much less lipogenically active, but also responded positively to thyroid hormone. Both hyper- and hypothyroidism diminished fatty acid synthesis in retroperitoneal fat and had similar, although not significant, effects in epididymal fat. However, epididymal adipocytes, taken from hyperthyroid rats and cultured in vitro, were 3 times more lipogenically active than cells from either hypo- or euthyroid animals. Lipogenesis in sc fat from hyperthyroid rats was enhanced when calculated per g tissue, but was not different when expressed per whole tissue. In brown adipose tissue, lipogenesis was inversely related to thyroid hormone status. Fatty acid synthesis in brain, lung, skin, and bone and muscle did not respond to changes in thyroid state. TLC confirmed that greater than 90% of the incorporated tritium was in fatty acids. Thus, in hypothyroid animals, lipogenesis primarily occurs in skin, bone, muscle, and other nonresponsive organs, whereas in hyperthyroid rats, the liver alone constitutes almost half of all fatty acid synthesis. The fatty acid synthetic pathway provides an excellent model for examining the tissue-specific regulation of gene expression by thyroid hormone.     

Reduced lipogenesis in rats fed a high-protein carbohydrate-free diet

Rates of fatty acid synthesis were assessed in carcass, liver, and adipose tissue from rats fed for 30 to 40 days a balanced diet (66% wt/wt carbohydrate, 17% casein, 8% fat) or a high-protein carbohydrate-free diet (70% casein, 8% fat). Despite similar body weight increases, carcass fatty acid content of rats on the high-protein (HP) diet was 13% less, and the weight of their epididymal fat pads was reduced by 29% in relation to the controls. In vivo incorporation of 3H2O into carcass fatty acids (FA) and into liver triacylglycerol (TAG) was significantly reduced in HP-fed rats. FA synthesis from 14C-acetate, glucose, or leucine and from 3H2O was also markedly decreased in liver slices from HP rats. The amount of 3H-TAG that accumulated in plasma of rats injected with triton WR 1339 to block peripheral utilization of lipoprotein corresponded in HP and control rats to only 4.1% and 5.0%, respectively, of 3H-FA recovered in carcasses from animals not treated with triton, indicating that almost all of the carcass 3H-TAG was synthesized in situ. However, on a long term basis, the reduced hepatic lipogenesis and the resulting decreased transport of TAG might affect lipid accumulation in HP rats. In vivo lipogenesis from 3H2O and in vitro FA synthesis from 3H2O and from 14C-precursors did not differ significantly in retroperitoneal and epididymal adipose tissue from HP and control rats. In both groups of animals, in vivo rates of lipogenesis were higher in retroperitoneal than in epididymal adipose tissue but still did not account for rates of FA synthesis by carcasses, suggesting the existence of other sites with higher lipogenic activity.     

Selective mobilisation of fatty acids from human adipose tissue

Background: Adipose tissue is a storage organ for dietary fat. During fasting, fatty acids are released into serum as free fatty acids (FFA). Experimental studies indicate that fatty acids are selectively mobilised from adipose tissue into serum. The aim of this study was to investigate whether the composition of the serum FFA fraction reflects selective mobilisation in the fasting state in humans. Methods: The fatty acid composition of fasting serum FFA and adipose tissue were analysed from 112 patients with myocardial infarction and 107 healthy control subjects using gas-liquid chromatography. The subjects' habitual diet was analysed using a food-frequency questionnaire. Results: Significant correlations were found between serum FFA and adipose tissue, particularly for the percentage content of linoleic acid (r=0.73), eicosapentaenoic acid (r=0.68), alpha-linolenic acid (r=0.67) and palmitoleic acid (r=0.60). Percentage contents of palmitic, stearic, linoleic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acid were higher in serum FFA than in adipose tissue, whereas oleic and palmitoleic acid were relatively more abundant in adipose tissue. This may indicate that the former group of fatty acids is preferentially mobilised from adipose tissue into serum. High correlations for polyunsaturated fatty acids were observed between percentage contents of dietary and adipose tissue fatty acids. The correlation of fatty acids between diet and serum FFA was weak, but a tendency towards higher correlations for polyunsaturated fatty acids was observed. Conclusions: Our findings are compatible with the hypothesis that, in the fasting state, fatty acids are selectively mobilised from adipose tissue into serum FFA.     

Polycystic ovary syndrome and adipose tissue

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women of reproductive age. Typically, it is associated with ovulatory dysfunction: dysovulation or anovulation, and symptoms of hyperandrogenism. It incurs risk of metabolic disorders such as diabetes, dyslipidemia and fatty liver. As a key endocrine organ in metabolic homeostasis, adipose tissue is often implicated in these complications. Studies of white adipose tissue (WAT) in PCOS have focused on the mechanism of insulin resistance in this tissue. Clinically, abnormalities in WAT distribution are seen, with decreased waist-to-hip ratio and increased ratio of adipose to lean mass. Such abnormalities are greater when total circulating androgens are elevated. At tissue level, white adipocyte hyperplasia occurs, along with infiltration of macrophages. Secretion of adipokines, cytokines and chemo-attractant proteins is increased in a pro-inflammatory manner, leading to reduced insulin sensitivity via alteration of glucose transporters, and hence decreased glucose uptake. The kinetics of non-esterified fatty acids (or free fatty acids) is also altered, leading to lipotoxicity. In recent years, brown adipose tissue (BAT) has been studied in women with PCOS. Although abundance is low in the body, BAT appears to play a significant role in energy expenditure and metabolic parameters. Both supra-clavicular skin temperature, which reflects BAT activity, and BAT mass are reduced in women with PCOS. Moreover, BAT mass and body mass index (BMI) are inversely correlated in patients. In the adipocyte, increased total circulating androgen levels reduce expression of uncoupling protein 1 (UCP1), a key protein in the brown adipocyte, leading to reduced biogenesis and mitochondrial respiration and hence a reduction in post-prandial thermogenesis. BAT is currently being investigated as a possible new therapeutic application.     

Effect of physical training on esterification of glycerol-3-phosphate by homogenates of liver,skeletal muscle,heart, and adipose tissue of rats

The effect of a physical training program on glyceride synthesis by homogenates of rat adipose tissue, muscle, heart, and liver was studied. One group of rats was trained by a 12-wk program of treadmill running, while another group served as sedentary controls. Training increased glycerol-3-phosphate esterification in adipose tissue (59%), skeletal muscle (27%), and heart (16%) but had no effect in liver. The results of this study indicate that training increased a synthetic pathway of lipid metabolism in muscle, providing further evidence that endogenous glycerides may provide a source of fatty acids during exercise. The effect of training on glyceride synthesis in adipose tissue indicates that an enhanced ability to esterify fatty acids in times of inactivity may be a biochemical adaptation enabling a trained animal to replenish an energy reserve that can be called upon in time of need.     

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.     

Compositional and metabolic changes in brown adipose tissue following a single test meal

In rats maintained on a scheduled feeding plan, the hypertrophy of brown adipose tissue (BAT) observed after a low-protein/high-carbohydrate single test meal was accompained by significant changes in the percentage of all major constituents of the tissue. There was a fall in the percentage of water (P < 0.01), a rise in the percentage of fat (P < 0.05), and a rise in the percentage of glycogen (P < 0.001). The largest absolute changes following a meal were in the fat content, which almost doubled, and in the glycogen content, which exhibited about a four-fold increase. Deposition of fat in the BAT following the test meal was accompanied by a three-fold increase in the rate of fatty acid synthesis (P < 0.05). The in vitro respiration rate of BAT was usually significantly increased in the meal-fed rats, but the effect of replacing the protein content of the test meal with starch was not clear. A lower protein, higher starch diet (9% of calories from protein, 72% from starch) resulted in a trend for a larger thermic effect than a higher protein, lower starch diet (27% of calories from protein, 54% from starch).