Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR.     

Ability of omega-3 fatty acids to restore the impaired glucose tolerance in a mouse model for type-2 diabetes. Different effects in male and female mice

Mice of both sexes were fed diets with 80 per cent animal or vegetable fat for 3 months. Half of the animals also received SuperEPA, which contains 61% omega-3 fatty acids. At the end of the feeding period the mice receiving animal fat had gained more weight than the controls and the mice receiving vegetable fat, and all fat diet groups, irrespective of sex or kind of diet, had become hyperglycaemic and had impaired intravenous glucose tolerance. The decay in plasma glucose during the tolerance tests was, however, significantly slower in the groups getting animal fat than in the groups getting vegetable fat. Supplementation with omega-3 fatty acids only affected the male mice receiving the animal fat diet. Thus, these mice gained less weight, and both the hyperglycaemia and the impairment of the glucose tolerance were significantly less pronounced in this group than in the male mice fed animal fat without SuperEPA. In the groups eating fat diets, the plasma total cholesterol levels increased 50-100 per cent during the first 2 weeks of the experiment and then plateaued. In both sexes HDL-cholesterol averaged approx. sixty-five per cent of the total cholesterol content at the start of the experiment and was not changed significantly during the feeding period. It is concluded, that omega-3 fatty acids do not seem to be suitable as a general means of ameliorating impaired glucose tolerance. It is further suggested that the fat-fed mouse may be a useful animal model for further studies of the regulation of metabolism in type-2 diabetes.     

Dietary self-selection vs. complete diet: body weight gain and meal pattern in rats.

Food intake and body weight gain of male adult Wistar rats were examined in two groups of animals. One group (n = 14) was allowed to select its diet from separate sources of protein (casein, 3.1 kcal/g), fat (lard and sunflower oil, 7.9 kcal/g) and carbohydrate (CHO, starch and sucrose, 3.3 kcal/g). Another group (n = 10) received a nutritionally complete diet (3.3 kcal/g). After 2 weeks of adaptation to the diets, body weights and meal patterns were recorded for at least 4 days. The total caloric intake was nearly identical for the two groups of rats. Rats given dietary choice gained less weight over 4 days than rats fed chow and showed reduced feed efficiency. During the 24-h period, self-selecting rats consumed 20.8% of calories as proteins, 21% as fats and 58.2% as CHO. Self-selecting rats ate significantly less calories during the day than did rats given chow. The chow diet consisting of 17.3% calories as protein, 7.6% as fat and 75.1% as CHO. When comparing the self-selecting group nutrient intakes to those of chow-fed group it was observed that 24-h protein calorie intakes were identical in both groups. Fat intake was significantly higher and CHO reduced as compared to chow-fed rats. During the day, CHO intake was higher in self-selecting rats, and fat intake was not significantly reduced. During the night, protein and fat intakes were significantly higher in self-selecting rats, while CHO intake was significantly decreased, particularly in the last periods of the night.(ABSTRACT TRUNCATED AT 250 WORDS)     

Norepinephrine turnover in brown and white adipose tissue after partial lipectomy

Total body fat is restored after the surgical removal (i.e., partial lipectomy) of white adipose tissue (WAT), and this is accomplished via increases in the mass of nonexcised WAT pads. The underlying mechanism for this apparent regulation of total body fat is unknown. One possibility is via the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) through the regulation of lipolysis and thermogenesis, respectively. Specifically, decreases in SNS activity might fuel lipectomy-induced body fat compensation through energy saved from decreased BAT thermogenesis and would promote lipid accretion through decreased WAT basal lipolysis. Therefore, we tested whether lipectomy triggered decreases in the SNS drive [as indicated by the norepinephrine turnover (NETO)] to nonexcised WAT or to BAT, at times before the lipectomy-induced fat pad mass compensation was complete. Siberian hamsters received either sham or bilateral epididymal WAT lipectomy, and NETO was measured in the remaining WAT and interscapular BAT (IBAT) before, and 3 and 6 weeks after surgery. Total dissected WAT, and inguinal and retroperitoneal WAT masses were significantly increased following lipectomy, whereas dorsal subcutaneous WAT and IBAT masses, as well as food intake, were unchanged. The only significant change in NETO was a marked decrease (approximately 90%) in IBAT NETO at Week 3 postlipectomy compared with the sham-lipectomized controls. These findings suggest that the lipid accretion of nonexcised WAT pads triggered by lipectomy may be partially fueled by decreased BAT thermogenesis, inasmuch as decreased IBAT NETO reflects decreased BAT heat production.     

Dietary obesity in adult and weanling rats following removal of interscapular brown adipose tissue

In order to investigate the role of brown adipose tissue (BAT) in diet-induced thermogenesis (DIT), a selection of palatable, energy-dense foods (Cafeteria diet) was used to increase the energy intakes of adult and weanling male rats, from some of which interscapular BAT (IBAT) had been surgically excised. Removal of IBAT had no effect upon energy intakes of the cafeteria-fed rats, nor of controls fed a pelleted stock diet. The rate of weight gain of intact controls was similar for the two diets, but adults with IBAT removed and fed with the cafeteria diet gained weight more rapidly than those fed the stock diet. Similarly, although intact weanlings did not exhibit excess weight gain when fed the cafeteria diet, removal of IBAT did result in more rapid weight gain of the cafeteria-fed weanlings relative to their stock-fed siblings. Nevertheless, total carcass energy was increased by some 20% in cafeteria-fed animals, irrespective of whether they had had IBAT removed. Thus there was no evidence for removal of IBAT having improved the efficiency of energy utilisation for growth. The failure to find evidence for altered levels of energy expenditure following removal of IBAT does not necessarily contradict the hypothesis that BAT mediates DIT, however, since, following removal of IBAT, there was hypertrophy of remaining BAT sites which may have compensated for the BAT removed.     

Effect of diet and animal care/housing protocols on body weight, survival, tumor incidences, and nephropathy severity of F344 rats in chronic studies

Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly (p<0.05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly (p<0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly (p<0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors.     

Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome

The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective strategy against insulin resistance and related situations.     

Smooth endoplasmic reticulum proliferation and increased cell multiplication in cultured hepatocytes of the newborn rat in the presence of phenobarbital

Twenty-eight-day old male Sprague-Dawley rats were fed diets containing 2, 5, 10, 15, 25, or 50% protein and varying levels of fat and energy for 8 weeks and were then killed. The livers of rats fed the 2% lactalbumin protein diet ad libitum but not the others showed visible fat. This difference was confirmed histologically. Chemical analyses of the livers indicated that the rats fed the 2% protein diets ad libitum had experienced a substantial reduction in liver cell size but only a very slight reduction in the lipid content of each cell. As a consequence, their livers showed a net increase in the amount of lipid per g of tissue and this gave them a fatty appearance. The lipids formed large fat globules suspended in a greatly reduced amount of protoplasm; there were no fat globules outside the cells. Therefore, the fatty liver of protein deficiency was a physical phenomenon rather than a metabolic defect. Rats fed the 2% protein diets in restricted amounts also had shrunken cells but they did not manifest fatty liver because there was a relatively greater reduction in liver cell lipid than in liver cell size. There was a reduced amount of protein in the livers of rats fed 2 and 5% protein diets which can be explained by a reduction in liver RNA and in Protein/RNA ratio. Protein/RNA ratio was enhanced by starvation. Liver protein content showed a biphasic response to variation in dietary fat level with its lowest value in rats fed diets containing 11.9% fat.     

Relation of types of dietary fat to cardiovascular damage in mice

Nine edible oils or fats (hydrogenated coconut, cod liver, Wesson, linseed, olive, butter, lard, corn and cocoa-butter) were fed for 50–90 days to study the relation of saturation, chain length and essential fatty acid content to production of cardiovascular lesions. The specific oil or fat (selected for ranges in the above variables) was used as the dietary lipid in a high-fat (28%), low-protein (8%), hypolipotropic diet. Half of the animals received identical diets containing choline chloride (2 gm/100 gm of diet) as a lipotropic supplement. Atrial mural thrombosis and ventricular myocardial necrosis and calcification developed in all dietary groups. Atrial thrombosis was the most frequent lesion. The greatest incidence of atrial thrombosis occurred in mice fed the choline-deficient, butter-containing diet (92%) and the lowest incidence with the supplemented cod liver oil diet (20%). The diet containing unsupplemented hydrogenated coconut oil produced the greatest incidence of ventricular necrosis (79%) and that with choline-supplemented cocoa-butter the lowest (8%). Ventricular calcification was most extensive within the unsupplemented cod liver oil group (83%), most limited in the supplemented lard group (5%). In general, choline-supplemented diets produced a lower incidence of cardiac damage. Little correlation existed between the composition and characteristics of specific fats and their activity in producing the specific cardiac lesions observed here.     

Concomitant food intake and adipose tissue responses under chronic insulin infusion in rats

Body weight (BW), food intake (FI), and activity of white adipose tissue (WAT) and brown adipose tissue (BAT) were studied in adult male rats under chronic insulin infusion. Insulin was infused for 4, 7 or 10 days via implanted minipumps. Insulin-treated rats gained more BW than control rats until 7th day of infusion. At 10 days, the difference in BW decreased. The average cumulative FI was significantly higher after 4, 7 and 10 days of insulin infusion. Feed efficiency (FE) was increased in insulin-treated rats after 4 and 7 days. An increase in WAT weight was observed in insulin-treated rats together with an increased activity of lipogenic enzymes. BAT weight was augmented after 4 days of insulin infusion. This was due mainly to lipid accumulation. Specific mitochondrial guanosine diphosphate (GDP) binding was significantly decreased by 58% in insulin-treated rats after 4 days of infusion. This reduced thermogenic activity, along with the increased FI and FE were responsible for the rapid BW gain observed during the first 7 days of insulin infusion.     

Preneoplastic and neoplastic lesions in the pancreas of rats fed choline-devoid or choline-supplemented diets

Groups of male Fischer 344 rats were chronically fed semipurified choline-devoid or choline-supplemented diets, high in fat (15%), and containing or not containing 0.06% phenobarbital. Atypical acinar cell nodules were observed in the pancreas of the rats, irrespective of the diet fed, with incidences varying from 38% to 100% in the various groups. No consistent differential effects of the dietary treatments on the incidence and growth of the nodules were evident, even though the diameter of the nodules tended to be greater in some of the groups fed the basal choline-devoid diet. The vast majority of the nodules were of the acidophilic type. More advanced pancreatic acinar cell lesions were observed in a few of the rats. Since the rats were not exposed to a chemical carcinogen(s), development of the nodules and of the more advanced lesions, even in rats fed the control diets, was most likely due to evolution of endogenous (spontaneous) initiated pancreatic cells, promoted primarily by the feeding of semipurified diets with a high fat content.     

Protein selection, food intake, and body composition in response to the amount of dietary protein

Though not universally observed, moderately low-protein diets have been found to increase caloric intake and body fat. It appears that animals overeat in calories in order to obtain more dietary protein. For animals to control protein intake, they must be able to distinguish between two isocaloric diets containing different percentages of protein and make the appropriate dietary selection on the basis of their previous history of protein intake. Experiment 1 examined the 24-h diet selection (5 vs. 35% casein) of Sprague-Dawley rats that had been previously fed diets containing various percentages of dietary protein (5, 10, 20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a preference for the higher protein selection diet. In contrast, no significant diet preference was found in animals pre-fed the two higher levels of dietary protein (35 or 60% casein). In this study, daily food intake and body fat of rats fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20% casein diet. Experiment 2 examined the effects of the level of methionine supplementation on rats fed 10% casein. In this study, food intake and body fat were increased by approximately 20% in rats fed 10% casein diets, regardless of the level of methionine supplementation (0.3 vs. 0.15%). Together, the results suggest that the presence of low-protein-induced hyperphagia helps maintain body protein levels in the face of moderately low dietary protein and promotes an increase in the amount of body fat and energy.     

Effect of hydroxycitrate on food intake and body weight regain after a period of restrictive feeding in male rats

We examined whether dietary supplementation of hydroxycitrate (HCA), a competitive inhibitor of the extramitochondrial enzyme ATP-citrate-lyase, which inhibits lipogenesis, reduces food intake and body weight regain in rats after 10-15% weight loss. In four experiments, 24 male rats were fed restrictively (10 g/day) for 10 days and then given ad lib access to one of four different diets (HI-Suc=high sucrose; HI-Glu=high glucose; Chow=grounded standard rat chow; HI-Glu+Fat=high glucose+fat) varying in the content of fat and low molecular carbohydrates for the following 10 days. For half of the rats (n=12), the ad lib diet was supplemented with 3% (w/w) HCA. HCA reduced body weight regain with all diets except Chow. HCA also reduced food intake temporarily with three of the four tested diets. The suppressive effect of HCA on food intake was particularly strong with the HI-Glu+Fat diet (fat=24% of energy). With Diet HI-Glu and HI-Glu+Fat HCA reduced the feed conversion efficiency (cumulative body weight regain (g)/cumulative food intake (MJ)) during the 10 ad lib days, suggesting that it also increased energy expenditure. This effect seemed to be positively related to the glucose content of the diet. All in all, HCA reduced body weight regain after substantial body weight loss, and the effects are presumably linked to its inhibiting effect on lipogenesis, but the exact mechanism still has to be determined.     

The relative protective effects of moderate dietary restriction versus dietary modification on spontaneous cardiomyopathy in male Sprague-Dawley rats

The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet. Serum lipids, carcass composition, and organ weights were evaluated and hearts were qualitatively and quantitatively examined microscopically for male SD rats at 1 and 2 years. Cardiomyopathy was characterized by the colocalization of myocardial degeneration, the development of subepicardial, perivascular, subendocardial, and interstitial fibrosis, and mononuclear inflammatory cell infiltration that increased by incidence and severity in an age-dependent manner from 1 to 2 years. SD rats fed the 5002 diet AL had the greatest heart weights and the most severe cardiomyopathy, with the highest myocardial fibrotic index. These parameters were relatively decreased in the AL 5002-9 diet, the DR 5002 diet, and the DR 5002-9 diet rats at 1 and 2 years. Regardless of the type of diet fed, both AL groups had the most severe cardiomyopathy by 2 years. Moderate DR allowed isocaloric comparisons of the relative effects of modified diets on survival, obesity, and heart disease. Only slight improvements in the severity and progression of spontaneous cardiomyopathy were seen by modification of the protein, fiber, fat, and energy content of the diet if fed AL. However, moderate DR with either diet was more effective than changing the diet composition in preventing and controlling the progression of cardiomyopathy in male SD rats.     

Glucocorticoids and regulation of phosphoenolpyruvate carboxykinase activity in rat brown adipose tissue.

Studied were performed to examine the factors that might regulate phosphoenolpyruvate carboxykinase (PEPCK) activity in rat brown adipose tissue (BAT) and to determine the role played by glucocorticoids in regulating this enzyme. Comparison was made to white adipose tissue (WAT) where PEPCK activity is known to be glucocorticoid regulated. PEPCK activity in BAT did not respond to adrenalectomy or dexamethasone, whereas WAT activity was increased and decreased, respectively, by these maneuvers. Three conditions were found in which BAT PEPCK activity was stimulated: 1) fasting, 2) feeding a high-fat/low-carbohydrate diet, and 3) during the neonatal period. In each case glucocorticoid treatment prevented the stimulation in PEPCK activity and restored the enzyme to base-line levels. In conditions 1 and 2, enzyme activity was also stimulated in WAT, but in contradistinction to BAT, glucocorticoid administration reduced activity to low levels significantly below base-line activity. Two conditions were found which suppressed PEPCK activity in BAT: exposure to a cold environment and feeding a high-protein/low-fat diet. WAT PEPCK was unaltered by exposure to cold. Thus, differences in PEPCK regulation between BAT and WAT were demonstrated, and the response to glucocorticoids was unique in BAT.     

不同脂肪含量的高脂纯化配方饲料对大、小鼠代谢综合征发生的影响

 摘要： 目的 探讨不同脂肪含量的高脂纯化配方饲料对大、小鼠体重、血糖、血胰岛素、血脂、脂肪肝及白蛋白尿的影响。 方法 雄性SD大鼠及C57BL/6小鼠随机分为MS10%、MS45%和MS60%脂肪含量饲料组,喂养3个月,检测动物体重、血糖、血胰岛素水平、血脂和蛋白尿水平,以及主要脏器重量及肝脏脂质含量。 结果 与正常组（MS10%脂肪含量）相比,高脂组（MS45%和MS60%脂肪含量）动物体重显著增加,出现明显的糖耐量异常、胰岛素抵抗和血脂水平升高,同时伴有肝脏脂质含量和蛋白尿水平的增加,并且以MS45%高脂组体重增加及胰岛素抵抗更加显著。 结论 MS45%和MS60%高脂配方饲料均可在大、小鼠较好地诱导代谢综合征的发生,而且前者优于后者。 关键词： 高脂饲料;胰岛素抵抗;肥胖;代谢综合征     

Insulin secretion to glucose stimulus in pancreatic islets isolated from rats fed unbalanced diets.

To verify the effect of different energetic sources on insulin secretion, just-weaned male Wistar rats were divided into four groups fed as follows: high carbohydrate (HC), high protein (HP), high lipid (HL) and balanced (C) diets during five weeks. Body weight gain and daily food intake were similar among the four groups. Insulin content of the isolated islets was not different; however, insulin release to a high glucose concentration (16.7 mM) stimulus was clearly higher in islets isolated from rats fed a balanced diet as compared to the other groups (HC, HP and HL). The rates of insulin secretion in islet perfusates from rats fed unbalanced diets were also decreased, although 45Ca2+ outflow rate (FOR) was similar in all groups. Since the rate of U-14C-glucose oxidation was decreased in islets isolated from rats fed unbalanced diets, this could be one of the mechanisms for the reduced rates of insulin release observed. Therefore, the increased supply of specific fuels provoke metabolic alterations in B-cell leading to changes in insulin secretion.     

Relationship between fatty liver and subsequent development of necrosis, inflammation and fibrosis in experimental alcoholic liver disease

Rats fed a diet varying in the amount of fat, infused with ethanol, were studied to determine the relationship among diet, degree of fatty liver, and development of necrosis, inflammation, and fibrosis. Three groups of experimental animals, male Wistar rats, were fed diets containing 25% fat, 35% fat, and 32% fat with low protein. Morphologic assessment of liver injury was performed monthly by obtaining liver biopsies. The greatest degree of fatty infiltration at 1 month was seen in the high fat-low protein group, the mean fat score (3.8 +/- 0.37) was significantly higher than in the other two groups (P less than 0.05 and P less than 0.01). When the subsequent development of necrosis, inflammation, and fibrosis was related to the degree of fatty infiltration at 1 month, a significant relationship was seen between the number of animals developing these pathologic lesions and the severity of fatty liver. Our results show that the degree of fatty infiltration of the liver, influenced by the dietary intake of both fat and protein, is related to the subsequent development of necrosis, inflammation, and fibrosis in our intragastric feeding model for alcoholic liver disease.     

Evaluation of brown adipose tissue with intermolecular double-quantum coherence magnetic resonance spectroscopy at 3.0 T

In the current study, we propose a single-voxel (SV) magnetic resonance spectroscopy (MRS) pulse sequence, based on intermolecular double-quantum coherence (iDQC), for in vivo specific assessment of brown adipose tissue (BAT) at 3 T. The multilocular adipocyte, present in BAT, typically contains a large number of small lipid droplets surrounded by abundant intracellular water, while the monolocular adipocyte, present in white adipose tissue (WAT), accommodates only a single large lipid droplet with much less water content. The SV-iDQC sequence probes the spatial correlation between water and fat spins at a distance of about the size of an adipocyte, thus can be used for assessment of BAT, even when mixed with WAT and/or muscle tissues. This sequence for measurement of water-to-fat (water-fat) iDQC signals was tested on phantoms and mouse BAT and WAT tissues. It was then used to differentiate adipose tissues in the supraclavicular and subcutaneous regions of healthy youth human volunteers (n = 6). Phantom results with water-fat emulsions demonstrated enhanced water-fat iDQC signal with increased voxel size, increased energy level of emulsification, or increased distribution balance of water and fat spins. The animal tissue experiments resulted in obvious water-fat iDQC signal in mouse BAT, while this signal was almost absent in the WAT spectrum. The optimal choice of the dipolar coupling distance for the observation was approximately 100 μm, as tested on both emulsion phantom and animal tissue. The water-fat iDQC signals observed in the supraclavicular adipose tissues were higher than in the subcutaneous adipose tissues in healthy young volunteers (0.43 ± 0.36 vs. 0.10 ± 0.06, p = 0.06). It was concluded that the iDQC-based sequence has potential for assessment of mouse and human BAT at 3 T, which is of interest for clinical research and the diagnosis of obesity and associated diseases.     

Comparison of DNA synthesis in white and brown adipose tissue in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic (VMH) lesions cause excessive fat accumulation in white adipose tissue (WAT), and brown adipose tissue (BAT); however, little information is available on whether or not cell proliferation occurs in WAT and BAT after VMH lesioning. In this study, we determined the DNA content and thymidine incorporation in unilateral parametrial WAT and interscapular BAT 0, 1, 3, and 7 days after VMH lesioning, and examined the mechanism of increased DNA content in WAT. In rats with VMH lesions, the weight of WAT and BAT had increased significantly at 7 days, and the DNA content and thymidine incorporation of WAT had increased significantly at 3 days and continued to increase for up to 7 days, while those of BAT did not increase for as long as 7 days after VMH lesioning. Restricted food intake according to the pair-feeding method partially inhibited the increased DNA content in WAT. The increased DNA content in WAT was mostly restored but not completely by the administration of anti-insulin antibody, and by administration of propranolol, a -adrenergic blocker. The results demonstrated that VMH lesions induced DNA synthesis in WAT early after VMH lesioning, but did not induce DNA synthesis in BAT, and suggested that either hyperinsulinemia or a -adrenergic receptor mechanism or both may be responsible for the increased DNA content in WAT.