Glucocorticoids in Adipocytes Stimulate Visceral Obesity

The enzyme 11 hydroxysteroid dehydrogenase-1 (11β HSD-1) regenerates active glucocorticoids from inactive glucocorticoids. When over-expressed in adipose tissue, this enzyme was shown to promote increased visceral adipose levels. The resulting visceral obesity was associated with insulin-resistant diabetes and dyslipidemia. Increased adipocyte 11β HSD-1 is a possible cause of visceral obesity in humans.     

Vitamin A supplementation ameliorates obesity-associated retinal degeneration in WNIN/Ob rats

ObjectiveObesity is associated with various health afflictions, including ocular complications such as diabetic retinopathy, high intraocular pressure, cataracts, and macular degeneration. We previously reported progressive retinal degeneration after the onset of obesity in the spontaneously obese rat (WNIN/Ob) model. In the present study, we investigated vitamin A supplementation to ameliorate obesity-associated retinal degeneration in the WNIN/Ob rat.MethodsFive-month-old male WNIN/Ob obese (O) and lean (L) control rats were fed with vitamin A 2.6 mg (L/O-I), 26 mg (L/O-II), 52 mg (L/O-III), and 129 mg (L/O-IV) per kilogram of diet as retinyl palmitate for 4 mo 2 wk. Retinal morphology and retinal gene expression were assessed by histologic, immunohistochemical, and real-time polymerase chain reaction methods.ResultsSupplementation of vitamin A at 26 or 52 mg significantly modulated the expression of retinal genes in the O but not in the L phenotype. Vitamin A supplementation significantly upregulated the expression of genes, such as rhodopsin, rod arrestin, phosphodiesterase, transducins, and fatty acid elongase-4, that were otherwise downregulated in O rat retina. The expression of glial fibrillary acidic protein was downregulated by vitamin A feeding in O rat retina. The immunohistochemical and histologic findings corroborated the gene expression data. The effects were significant at a 26- or 52-mg dose of vitamin A.ConclusionVitamin A supplementation alleviated obesity-associated retinal degeneration in the WNIN/Ob rat.     

Effects of Avocado Oil Supplementation on Insulin Sensitivity,Cognition, and Inflammatory and Oxidative Stress Markers in Different Tissues of Diet-Induced Obese Mice

Obesity induces insulin resistance, chronic inflammation, oxidative stress, and neurocognitive impairment. Avocado oil (AO) has antioxidants and anti-inflammatory effects. This study evaluated the effect of AO supplementation on obese mice in the adipose tissue, muscle, liver, and hippocampus. Male C57BL/6J mice received a standard and high-fat diet (20 weeks) and then were supplemented with AO (4 mL/kg of body weight, 90 days) and divided into the following groups: control (control), control + avocado oil (control + AO), diet-induced obesity (DIO), and diet-induced obesity + avocado oil (DIO + AO) (n = 10/group). AO supplementation was found to improve insulin sensitivity and decrease hepatic fat accumulation and serum triglyceride levels in DIO mice. AO improved cognitive performance and did not affect mood parameters. Oxidative marker levels were decreased in DIO + AO mice in all the tissues and were concomitant with increased catalase and superoxide dismutase activities in the epididymal adipose tissue and quadriceps, as well as increased catalase activity in the liver. AO in obese animals further induced reductions in TNF-α and IL-1β expressions in the epididymal adipose tissue and quadriceps. These results suggest that AO supplementation has the potential to be an effective strategy for combating the effects of obesity in rats, and human studies are needed to confirm these findings.     

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese,hyperlipidemic OLETF Rats

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9 cis, 11 trans, 13 cis -conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.     

Altered or impaired immune response upon vaccination in WNIN/Ob rats

The present study was aimed to study the immune response in three months old male and female naïve obese animals and upon hepatitis B vaccination in three months old female WNIN/Ob obese mutant rats, established at our institute in comparison with its lean litter mates. Altered immune profile was seen in naïve obese mutant rats in terms of percentage of splenic CD8⁺ cytotoxic cells in males and percentages of splenic CD3⁺ T lymphocytes and CD4⁺ T helper cells in females respectively. Furthermore these obese mutant rats also exhibited impaired immune response to hepatitis B vaccine with low specific Hepatitis B surface antigen (HBsAg) specific IgG response and splenic lymphocyte proliferative response to HBsAg compared to the lean counterpart. The loss of immunological memory following vaccination could be attributed to the metabolic and hormonal changes associated with obesity. This observation has implication in public health policies related to vaccination in developed as well as developing countries.     

Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats

Background: Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on obesity accelerates ageing. Present study validated the hypothesis, ‘super-imposing T2D on obesity accelerates ageing’ in WNIN/Gr-Ob, the impaired glucose tolerant, obese rat as the model and evaluated probable underlying mechanisms.

Objectives: To estimate the survival analysis of WNIN/Gr-Ob rats induced with T2D. To determine the extent of DNA damage and oxidative stress in the brain, the master controller of the body, in WNIN/Gr-Ob rats with/without high sucrose induced T2D/aggravation of insulin resistance (IR) after 3 and 6 months of feeding.

Methods: T2D was induced/IR was aggravated by feeding high sucrose diet (HSD) to 9–10 weeks old, male WNIN/Gr-Ob rats. Survival percentage was determined statistically by Kaplan–Meier estimator. Neuronal DNA damage was quantified by the Comet assay while the oxidative stress and antioxidant status were evaluated from the levels of malonaldialdehyde, reduced glutathione, and superoxide dismutase (SOD) activity.

Results and Discussion: HSD feeding decreased longevity of WNIN/Gr-Ob rats and was associated with significantly higher total neuronal DNA damage after three months of feeding but not later. In line with this was the increased neuronal oxidative stress (lipid peroxidation) and decreased antioxidant status (reduced glutathione and SOD activity) in HSD than Starch-based diet (SBD) fed rats. The results suggest that HSD feeding decreased the longevity of WNIN/Gr-Ob obese rats probably by increasing oxidative stress and aggravating IR, a condition that precedes T2D.     

Site-specific differences in the fatty acid composition of abdominal adipose tissue in an obese population from a Mediterranean area: relation with dietary fatty acids, plasma lipid profile, serum insulin, and central obesity.

BACKGROUND: Abdominal obesity is associated with coronary risk, although causality is not well established. OBJECTIVE: In an obese Mediterranean population, we measured the fatty acid composition of adipose tissue, its relation with dietary fatty acids and central fat deposition, and its influence on plasma lipids and insulin. DESIGN: Adipose tissue samples were obtained from 84 obese patients (29 men, 55 women) aged 30-70 y (body mass index, in kg/m(2): 27-35). We measured concentrations of insulin and lipids in plasma and fatty acids in subcutaneous, omental, and perivisceral fat. Dietary fatty acid intake was assessed with a 7-d diet record. RESULTS: The population studied was normolipidemic and normoinsulinemic. There were important differences in fatty acid composition between tissue sites: saturated fatty acids were higher and monounsaturated fatty acids were lower in perivisceral than in subcutaneous fat (P < 0.05). Significant correlations were found for oleic, linoleic, alpha-linolenic, and total n-6 polyunsaturated fatty acids between the subject's habitual diet and adipose tissue composition. Oleic and n-3 fatty acids from adipose regions were negatively correlated with apolipoprotein B and triacylglycerols; adipose tissue 22:1n-9, 20:2n-6, stearic acid, and eicosapentaenoic acid were positively correlated with HDL and apolipoprotein A; and adipose tissue myristic acid was negatively correlated with apolipoprotein A (P < 0.05). Central obesity was positively associated with n-6 polyunsaturated fatty acids and inversely associated with monounsaturated fatty acids and n-3 polyunsaturated fatty acids in adipose tissue (P < 0.05). CONCLUSION: The differences found in the composition and metabolism of perivisceral, omental, and subcutaneous fats may indicate that their atherogenic capacities also differ.     

Protection of Sodium Arsenite-Induced Ovarian Toxicity by Coadministration of L-Ascorbate (Vitamin C) in Mature Wistar Strain Rat

Arsenic, a major water pollutant in India, produces toxic effects on female reproductive system in rodent models at the dose available in drinking water in arsenic-intoxicated zones. This study examines the coadministration of L-ascorbate (vitamin C) on ovarian steroidogenesis, plasma levels of gonadotrophins, brain monoamines, and ovarian as well as uterine peroxidase activities in sodium arsenite–treated rats. After sodium arsenite treatment, relative ovarian and uterine weights, ovarian Δ⁵-3β-HSD and 17β-HSD activities, plasma levels of gonadotrophins, norepinephrine levels in midbrain and diencephalon, and the activities of peroxidase in ovary and uterus were decreased significantly. On the other hand, serotonin levels in midbrain and diencephalon were increased significantly 28 days after sodium arsenite treatment at the dose of 0.4 ppm/100 g body weight/rat/day. All these parameters were protected significantly and in most cases were unchanged from control level when L-ascorbate at 25 mg/100 g body weight/rat/day was coadministered orally with sodium arsenite. This cotreatment of L-ascorbate with sodium arsenite also restored the estrous cycle in a regular manner. We concluded that L-ascorbate plays a pivotal role in maintaining normal ovarian activities and brain monoamines in arsenic-treated rats. Received: 22 May 2000/Accepted: 21 January 2001     

Extra-adrenal regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1: physiological regulator and pharmacological target for energy partitioning

The major glucocorticoid in man, cortisol, plays important roles in regulating fuel metabolism, energy partitioning and body fat distribution. In addition to the control of cortisol levels in blood by the hypothalamic-pituitary-adrenal axis, intracellular cortisol levels within target tissues can be controlled by local enzymes. 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the regeneration of active cortisol from inert cortisone, thereby amplifying cortisol levels and glucocorticoid receptor activation in adipose tissue, liver and other tissues. 11Beta-HSD1 is under complex tissue-specific regulation and there is evidence that it adjusts local cortisol concentrations independently of the plasma cortisol concentrations, e.g. in response to changes in diet. In obesity 11beta-HSD1 mRNA and activity in adipose tissue are increased. The mechanism of this up-regulation remains uncertain; polymorphisms in the HSD11B1 gene have been associated with metabolic complications of obesity, including hypertension and type 2 diabetes, but not with obesity per se. Extensive data have been obtained in mice with transgenic over-expression of 11beta-HSD1 in liver and adipocytes, targeted deletion of 11beta-HSD1, and using novel selective 11beta-HSD1 inhibitors; these data support the use of 11beta-HSD1 inhibitors to lower intracellular glucocorticoid levels and treat both obesity and its metabolic complications. Moreover, in human subjects the non-selective 'prototype' inhibitor carbenoxolone enhances insulin sensitivity. Results of clinical studies with novel potent selective 11beta-HSD1 inhibitors are therefore eagerly awaited. The present article focuses on the physiological role of glucocorticoids in regulating energy partitioning, and the evidence that this process is modulated by 11beta-HSD1 in human subjects.     

Lipolysis in intraabdominal adipose tissues of obese women and men

Intraabdominal fat in humans is located in two major depots, the omental and mesenteric. We compared basal and stimulated lipolysis in adipose tissue from these two depots and the subcutaneous abdominal depot of obese women and men. Omental fat cells of women are smaller and have lower rates of basal lipolysis than in men. Basal lipolysis rates are significantly higher in subcutaneous than intraabdominal adipose tissues of both genders. In men, the incremental lipolytic response to norepinephrine is significantly greater in both intraabdominal fat depots than in the subcutaneous fat, while in women the response of the mesenteric is lower than the omental. In women, but not men, responsiveness to the beta agonist isoproterenol is also increased in omental tissue. Thus, in women, omental and mesenteric adipose tissues show distinctly different metabolic properties which may moderate the impact of intraabdominal obesity.     

Leptin enhances the synthesis of oleoyl-estrone from estrone in white adipose tissue

Summary Background: Oleoyl-estrone elicits powerful slimming effects on lean and obese rats, sparing protein, lowering appetite and maintaining energy expenditure. Leptin synthesis is markedly reduced by oleoyl-estrone. However, this effect is not observed in the obese Zucker fa/fa rats; these rats do not fully respond to leptin but they lose fat under oleoyl-estrone treatment. Aim of the study: To determine the role of leptin in the conversion of estrone to fatty-acyl estrone in white adipose tissue both in vivo in Zucker lean and obese rats, and in vitro. Methods: Two series of experiments were performed: a) Growth and differentiation of 3T3L1 preadipocytes into adipocytes followed by incubation with tritium-labeled estrone in the medium in the presence / absence of 1 nM leptin, and estimation of the incorporation of label into estrone and estrone ester fractions of cell extracts. b) Zucker lean (Fa/?) [ZL] and obese (fa/fa) [ZO] rats were injected i.v. with carrier-free oleoyl-estrone in chylomicra-sized liposomes, then euthanized after 10 min. Free and esterified estrone were measured in blood, liver, muscle, skin, white adipose tissue (WAT), and brown adipose tissue(BAT). Results: In the first study, in a 72-h incubation, adipocytes took up 20-27% of the medium estrone. In the leptin(−) controls, 47% of the label in the cell fraction was in the form of estrone esters and 45% as free estrone; in the leptin (+) cells, 71% of the label was in the estrone ester fraction and 24% was free estrone. In the second study, a large part of the injected tritium-label remained in the ZO blood, with only a small part remaining in ZL. In ZL 39% of the label was found in the tissues in the form of free estrone, and in ZO only 22%; in both cases about half of it was in WAT. Plasma free estrone levels were 0.3±0.1 nM in ZL and 0.5±0.3 nM in ZO, and esterified estrone was 242±99 nM for ZL and 201±29 nM for ZO. Plasma leptin levels were 1.73±0.16 ng/ml in ZL and 61.0±1.4 ng/ml in ZO. Conclusion: The presence of an intact leptin pathway is critical for the uptake and synthesis of estrone esters as well as for the plasma acyl-estrone turnover. The presented results show a direct relationship between oleoyl-estrone and leptin in the WAT. A fully functional leptin pathway is needed for the synthesis of acyl-estrone and the removal of free estrone from the bloodstream, as well as for the disposal of excess circulating oleoyl-estrone. This has a direct bearing on human and animal obesity, since estrone induces increases in fat deposition.     

Diurnal changes in adipose and liver tissue metabolism of lean and obese Zucker rats

Metabolic adaptations to cyclic patterns of food intake were studied in genetically lean and obese Zucker rats. Twenty-four lean and 24 obese rats were exposed to 12 hours of light and 12 hours of dark and allowed food ad libitum. Both groups of rats ate more during the dark period of the cycle. The obese consumed nearly twice as much food as the lean during the light period of the cycle. At 4-hour intervals, rats were killed and liver and epididymal fat pads were removed for metabolic studies. Adipose tissue from lean rats demonstrated marked changes in rates of lipogenesis during the 24-hour cycle whereas adipose tissue from obese rats maintained a relatively steady rate of lipogenesis. Glucose incorporation into the glycerol moiety of triacylglycerol was nearly 3-fold higher in adipose tissue from obese rats. Liver lipogenesis in lean and obese rats followed their food intake pattern. Liver lipogenic rate (expressed per organ) was 3- to 5-fold higher in obese than lean rats during most of the 24-hour cycle. These data support the concept that the excessive fatty acids produced in the liver of obese rats are being esterified by adipose cells. Lipolytic response to glucagon was found in adipose tissue from obese rats during the dark and light periods, but only during the dark period for lean rats. These data suggest, in comparison to lean rats, that obese rats do not enter a relative catabolic state during a 24-hour cycle. A constant anabolic state in the genetically prone individual may lead to excessive lipid deposition and obesity.     

Organochlorine Pesticide Gradient Levels Among Maternal Adipose Tissue,Maternal Blood Serum and Umbilical Blood Serum

The objective of the present study was to determine levels and calculate ratios of copartition coefficients among organochlorine pesticides β-HCH, pp′DDE, op′DDT and pp′DDT in maternal adipose tissue, maternal blood serum and umbilical blood serum of mother-infant pairs from Veracruz, Mexico. Organochlorine pesticides were analyzed in 70 binomials: maternal adipose tissue, maternal serum and umbilical cord serum samples, using gas chromatography with electron capture detection (GC-ECD). The results were expressed as mg/kg on fat basis. p,p′-DDE was the major organochlorine component, detected in every maternal adipose tissue (0.770 mg/kg), maternal serum sample (5.8 mg/kg on fat basis) and umbilical cord blood sample (6.9 mg/kg on fat basis). p,p′-DDT was detected at 0.101 mg/kg, 2.2 mg/kg and 5.9 mg/kg respectively, according to the order given above. β-HCH was detected at 0.027 mg/kg, 4.2 mg/kg and 28.0 mg/kg respectively. op′DDT was detected only in maternal adipose tissue at 0.011 mg/kg. The copartition coefficients among samples identify significant increases in concentrations from adipose tissue to maternal blood serum and to umbilical blood serum. The increase indicated that maternal adipose tissue released organochlorine pesticides to blood serum and that they are carried over to umbilical cord blood.     

Polybrominated diphenyl ethers in Swedish human liver and adipose tissue

Paired samples of human liver and adipose tissue were analyzed for polybrominated diphenyl ethers (PBDEs) containing 3–6 bromine atoms. The samples were obtained at autopsy from one woman and four men at the age of 47 and 66–83 years, respectively. PBDEs were found in all samples. The sum of nine PBDE congeners ranged 5–18 ng/g lipids and 4–8 ng/g lipids in liver and adipose tissue, respectively. In three paired samples the concentrations were similar in liver and adipose tissue, while in two of the pairs the concentrations were higher in liver than in adipose tissue. The PBDE congeners 2,2′,4,4′-tetraBDE (BDE-47), 2,2′,4,4′,5-pentaBDE (BDE-99), and 2,2′,4,4′,5,5′-hexaBDE (BDE-153) occurred at highest levels and constituted together 87–96% and 84–94% of the total sum of PBDEs in liver and adipose tissue, respectively. The levels of PBDEs were compared to those of polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (p,p′-DDE), and hexachlorobenzene (HCB). Received: 13 June 2000/Accepted: 1 October 2000     

下丘脑腹内侧核损伤性肥胖大鼠动力相脂肪代谢研究

目的 :　探讨下丘脑腹内侧核损伤性肥胖大鼠在肥胖形成动力相中脂肪合成与分解代谢的变化。方法 :　雌性 SD大鼠分为下丘脑腹内侧核损伤肥胖组 (VMH)和下丘脑腹内侧核非损伤对照组 (sham) ,于下丘脑腹内侧核损伤和伪性损伤 1 w后 ,留取肝脏、皮下脂肪、子宫外周和肠系膜脂肪组织以及腓肠肌分别测定脂肪合成和分解酶活性。结果 :　VMH组大鼠肝脏微粒体甘油三酯转运蛋白、肝脏以及子宫外周和肠系膜脂肪组织的磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶活性均高于对照组。与对照组相比 ,VMH组子宫外周和肠系膜脂肪组织激素敏感脂酶(HSL )活性没有变化 ,皮下脂肪组织的 HSL活性升高 ,相反腓肠肌的 HSL活性下降。在 VMH组 ,皮下脂肪组织、子宫外周脂肪组织、肠系膜脂肪组织以及腓肠肌中的脂蛋白脂酶活性均升高。结论 :　在动力相 ,VMH肥胖大鼠肝脏合成和转运甘油三酯能力 ,以及脂肪组织如子宫外周和肠系膜脂肪组织的脂质合成和储存增强 ;另一方面 ,肌肉组织和皮下脂肪组织的脂肪分解也增强。     

Regional fat pad growth and cellularity in obese zucker rats: modulation by caloric restriction

OBJECTIVE: To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1). parameters of nonadipose and adipose growth, 2). regional adipose depot cellularity [fat cell volume (FCV) and number], and 3). circulating leptin levels. RESEARCH METHODS AND PROCEDURES: Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese-restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer-driven automated feeding system designed to mimic natural eating patterns. RESULTS: After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats. DISCUSSION: Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue-specific controls override the general consequences of food restriction in this genetic model of obesity.     

Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.