Postweaning low-calcium diet promotes later-life obesity induced by a high-fat diet

The aim of this study was to investigate the effects of a postweaning low-calcium diet on later obesity and explore the underlying mechanisms. Ninety-six male rats were weaned at 3 weeks of age, fed standard (STD: 0.50% calcium, n=48) and low-calcium (LC: 0.15% calcium, n=48) diets for 3 weeks, and then fed the standard diet for a 3-week washout period successively. Finally, the STD rats were divided into STD control and high-fat diet (HFD) groups, and the LC ones into LC control and LC+HFD (LCHF) groups. The STD and LC rats were fed the standard diet, while the HFD control and LCFD ones were fed a high-fat diet for 6 weeks to induce obesity. During the three feeding periods, adenosine-monophosphate-activated protein kinase (AMPK) and its responsive proteins phospho-acetyl-coA carboxylase, carnitine palmitoyltransferase 1 and uncoupling protein 3 were persistently down-regulated in the LC group (decreased by 18%, 24%, 18% and 20%, respectively) versus the STD group, and these effects were significantly more pronounced in the LCHFD group (decreased by 21%, 30%, 23% and 25%, respectively) than the HFD group by a later high-fat stimuli, causing more fat and body weight in adulthood. However, lipolysis enzymes, serum leptin, insulin and lipids were not significantly affected until the body weight and fat content changed at 15 weeks of age. The results suggest that the low-calcium diet after weaning promotes rat adult-onset obesity induced by high-fat diet, which might be achieved by programming expressions of genes involved in AMPK pathway.     

Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice

The Clock gene is a core component of the circadian clock in mammals. We show here that serum levels of triglyceride and free fatty acid were significantly lower in circadian Clock mutant ICR than in wild-type control mice, whereas total cholesterol and glucose levels did not differ. Moreover, an increase in body weight induced by a high-fat diet was attenuated in homozygous Clock mutant mice. We also found that dietary fat absorption was extremely impaired in Clock mutant mice. Circadian expressions of cholecystokinin-A (CCK-A) receptor and lipase mRNAs were damped in the pancreas of Clock mutant mice. We therefore showed that a Clock mutation attenuates obesity induced by a high-fat diet in mice with an ICR background through impaired dietary fat absorption. Our results suggest that circadian clock molecules play an important role in lipid homeostasis in mammals.     

不同配方益生菌在高脂饮食诱导小鼠肥胖发生中的差异化作用

【目的】基于肠道微生物与宿主代谢的相互关系,研究不同配方的益生菌对小鼠肥胖的影响。【方法】50只C57BL/6J雄性小鼠随机平均分成10组,分别给予正常饲料、高脂饲料以及高脂饲料加8种不同配方的益生菌产品(50亿CFU/只),所有动物连续喂养9周,每周测量小鼠体重1次。最后一周测定空腹血糖、葡萄糖耐量试验(glucose tolerance test,GTT)、血脂相关指标,称取内脏重量,并留取小鼠盲肠内容物,提取小鼠肠道菌群总DNA,利用16S rDNA测序检测相关细菌含量。【结果】部分益生菌可引起小鼠体重增速加快,而部分益生菌可减缓小鼠肥胖和降低内脏脂肪重量,同时缓解高血脂症。丹尼斯克品牌益生菌配方组小鼠肠道中厚壁菌/拟杆菌比例(F/B)是正常饮食组的22.8倍,Akkermansia muciniphila(Akkermansia)细菌含量几乎为0;而菌拉丁品牌益生菌配方组小鼠F/B比例与正常饲料饮食组类似,Akkermansia含量为0.5%,为正常饮食对照组小鼠的一半左右。【结论】益生菌可影响小鼠体重和代谢,但不同配方的益生菌效果截然相反。特定的益生菌配方对肥胖和高血脂的改善可能是由于其选用的菌株本身的特性以及菌株之间的相互配比能够降低小鼠肠道中F/B比例以及升高Akkermansia的含量所带来的。此研究为进一步开发可改善代谢的益生菌产品提供了参考。     

Wu-Mei-Wan prevents high-fat diet-induced obesity by reducing white adipose tissue and enhancing brown adipose tissue function

BackgroundWu-Mei-Wan, a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Our previous study showed that WMW treatment can prevent T2DM in db/db mice, which motivating the application of WMW on metabolic disorders.PurposeObesity and its comorbid diseases have increased dramatically and are now a worldwide health problem. There is still a lack of satisfactory treatment strategies for obesity. This work was designed to assess the effect and related mechanism of WMW on high fat diet (HFD)-induced obese mice model.MethodsObese mice were induced by HFD. Thetherapeutic effect of WMW were analyzed by examining body and adipose tissue weight, metabolic profile and energy expenditure. Adipose tissue phenotype was determined by histological staining and the mitochondrial content was examined by transmission electron microscopy (TEM). Immunohistochemical and immunofluorescence staining, RT-qPCR and Western blot analysis were used to evaluate expression of key molecules in adipose tissue.ResultsWMW treatment significantly protects HFD-induced obesity. Here we showed that WMW limits weight gain, improves metabolic profile and increases energy expenditure. WMW inhibits the hypertrophy and hyperplasia of white adipocytes, the mechanism involving the inhibition of TLR3/IL-6/JAK1/STAT3 pathway. In brown adipose tissue (BAT), WMW promotes thermogenicprogramme without affecting cell proliferation. The activated BMP7/ Smad1/5/9 pathway is considered to be one of the explanations for the effect of WMW on BAT.ConclusionOur results suggested that WMW can prevent obesity and its underlying mechanisms are associated with reducing white adipose tissue and enhancing brown adipose tissue function.     

Increased exercise capacity after surgically induced weight loss in morbid obesity

Objective: To investigate the effects of surgically induced weight loss on exercise capacity in patients with morbid obesity (MO). Research Methods and Procedures: A prospective 1‐year follow‐up study was carried out, with patients being their own controls. A symptom‐limited cardiopulmonary exercise stress test was performed in 31 MO patients (BMI > 40 kg/m²) before and 1 year after undergoing bariatric surgery. Results: At 1 year after surgery, weight was reduced from 146 ± 33 to 95 ± 19 kg (p < 0.001), and BMI went from 51 ± 4 to 33 ± 6 kg/m² (p < 0.001). After weight loss, obese patients performed each workload with lower oxygen consumption, heart rate, systolic arterial pressure, and ventilatory volume (p < 0.001). This reduced energy expenditure allowed them to increase the duration of their effort test from 13.8 ± 3.8 to 21 ± 4.2 minutes (p < 0.001). Upon finishing the exercise, MO patients before surgery were able to reach only 83% of their age‐predicted maximal heart rate, and their respiratory exchange ratio was 0.87 ± 0.06. After weight loss, those values were 90% and 1 ± 0.08, respectively (p < 0.01). When we compared the peak O₂ pulse corrected by fat free mass before and after surgery, no significant differences between the groups were found. Discussion: After surgically induced weight loss, MO patients markedly improved their exercise capacity. This is due to the fact that they were able to perform the external work with lower energy expenditure and also to increase cardiovascular stress, optimizing the use of cardiac reserve. There were no differences in cardiac function before and after surgery.     

Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism

The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.     

Alterations in pulmonary surfactant after rapid arousal from torpor in the marsupial Sminthopsis crassicaudata.

Torpor in the dunnart, Sminthopsis crassicaudata, alters surfactant lipid composition and surface activity. Here we investigated changes in surfactant composition and surface activity over 1 h after rapid arousal from torpor (15-30 degrees C at 1 degrees C/min). We measured total phospholipid (PL), disaturated PL (DSP), and cholesterol (Chol) content of surfactant lavage and surface activity (measured at both 15 and 37 degrees C in the captive bubble surfactometer). Immediately after arousal, Chol decreased (from 4.1 +/- 0.05 to 2.8 +/- 0.3 mg/g dry lung) and reached warm-active levels by 60 min after arousal. The Chol/DSP and Chol/PL ratios both decreased to warm-active levels 5 min after arousal because PL, DSP, and the DSP/PL ratio remained elevated over the 60 min after arousal. Minimal surface tension and film compressibility at 17 mN/m at 37 degrees C both decreased 5 min after arousal, correlating with rapid changes in surfactant Chol. Therefore, changes in lipids matched changes in surface activity during the postarousal period.     

Okara, soybean residue, prevents obesity in a diet-induced murine obesity model

We examined the effect of okara on the prevention of obesity in mice. A modified AIN-76 diet with a high fat content (14.1% of crude fat) was used as a basal diet. Male ICR mice were fed ad libitum with the basal diet or a dried okara-supplemented basal diet (10, 20, or 40%) for 10 weeks. The okara intake dose-dependently suppressed the development of body weight and epididymal white adipose tissue (EWAT), and prevented an increase of plasma lipids, including total cholesterol, LDL cholesterol, and non-esterified fatty acid. The okara intake also prevented steatosis in the liver. Real-time RT-PCR revealed that the okara intake induced down-regulation of the fatty acid synthetase gene and up-regulation of the cholesterol 7 alpha-hydroxylase (CYP7A1) gene in the liver. We also found that the okara intake caused a marked reduction in the expression of leptin and TNF-alpha genes in EWAT. Our results suggest that okara is beneficial in preventing obesity.     

Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice

Obesity is a major health concern worldwide which is associated with increased risk of chronic diseases such as metabolic syndrome, cardiovascular disease and cancer. The elucidation of the molecular mechanisms involved in adipogenesis and obesogenesis is of essential importance as it could lead to the identification of novel biomarkers and therapeutic targets for the development of anti-obesity drugs. MicroRNAs (miRNAs) have been shown to play regulatory roles in several biological processes. They have become a growing research field and consist of promising pharmaceutical targets in various fields such as cancer, metabolism, etc. The present study investigated the possible implication of miRNAs in adipose tissue during the development of obesity using as a model the C57BLJ6 mice fed a high-fat diet.C57BLJ6 wild type male mice were fed either a standard (SD) or a high-fat diet (HFD) for 5 months. Total RNA was prepared from white adipose tissue and was used for microRNA profiling and qPCR.Twenty-two of the most differentially expressed miRNAs, as identified by the microRNA profiling were validated using qPCR. The results of the present study confirmed previous results. The up-regulation of mmu-miR-222 and the down-regulation of mmu-miR-200b, mmu-miR-200c, mmu-miR-204, mmu-miR-30a*, mmu-miR-193, mmu-miR-378 and mmu-miR-30e* after HFD feeding has also been previously reported. On the other hand, we show for the first time the up-regulation of mmu-miR-342-3p, mmu-miR-142-3p, mmu-miR-142-5p, mmu-miR-21, mmu-miR-146a, mmu-miR-146b, mmu-miR-379 and the down-regulation of mmu-miR-122, mmu-miR-133b, mmu-miR-1, mmu-miR-30a*, mmu-miR-192 and mmu-miR-203 during the development of obesity. However, future studies are warranted in order to understand the exact role that miRNAs play in adipogenesis and obesity.     

Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain

The role of serine/threonine protein phosphatase 5 (PP5) in the development of obesity and insulin resistance associated with high-fat diet-feeding (HFD) was examined using PP5-deficient mice (Ppp5c^−/−). Despite similar caloric intake, Ppp5c^−/− mice on HFD gained markedly less weight and did not accumulate visceral fat compared to wild-type littermates (Ppp5c^+/+). On a control diet, Ppp5c^−/− mice had markedly improved glucose control compared to Ppp5c^+/+ mice, an effect diminished by HFD. However, even after 10 weeks of HFD glucose control in Ppp5c^−/− mice was similar to that observed in Ppp5c^+/+ mice on the control diet. Thus, PP5 deficiency confers protection against HFD-induced weight gain in mice.     

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet.     

Foenumoside B from Lysimachia foenum-graecum inhibits adipocyte differentiation and obesity induced by high-fat diet

We have previously reported anti-obesity effects of Lysimachia foenum-graecum in high-fat diet (HFD)-induced obesity model. Here we isolated a triterpene saponin foenumoside B as an active component of L. foenum-graecum. Foenumoside B blocked the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner with an IC50 of 0.2 μg/ml in adipogenesis assay and suppressed the induction of PPARγ, the master regulator of adipogenesis. Foenumoside B induced the activation of AMP-activated protein kinase (AMPK), and modulated the expression of genes involved in lipid metabolism towards lipid breakdown in differentiated adipocytes. In mouse model, oral administration of foenumoside B (10mg/kg/day for 6 weeks) reduced HFD-induced body weight gain significantly without affecting food intake. Treatment of foenumoside B suppressed lipid accumulation in white adipose tissues and the liver, and lowered blood levels of glucose, triglycerides, ALT, and AST in HFD-induced obese mice. Consistent with the in vitro results, foenumoside B activated AMPK signaling, suppressed the expression of lipogenic genes, and enhanced the expression of lipolytic genes in vivo. Foenumoside B also blocked HFD-induced proinflammatory cytokine production in adipose tissue, suggesting its protective role against insulin resistance. Taken together, these findings demonstrate that foenumoside B represents the anti-obesity effects of L. foenum-graecum, and suggest therapeutic potential of foenumoside B in obesity and obesity-related metabolic diseases.     

Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet

The objective of this study was to investigate meal-related endocrine changes that permit one to identify Sprague-Dawley rats at normal weight that are prone (OP) vs. resistant (OR) to obesity. In blood collected via chronic cardiac catheters, a 2-h high-fat meal (HFM, 50% fat, 40 kcal) at dark onset caused a significant increase in leptin, insulin, and triglycerides compared with premeal levels. Similar to patterns in already obese compared with lean rats on a high-fat diet, these meal-induced endocrine changes in normal-weight rats on lab chow were almost twofold larger in OP rats that, compared with OR rats, subsequently accumulated 100% more fat mass on a chronic high-fat diet. These exaggerated endocrine changes were similarly observed in blood collected using a simpler tail vein puncture procedure. In three separate experiments, the HFM-induced rise in leptin was found to be the strongest, positive correlate (r = +0.58, +0.62 and +0.64) of long-term body fat accrual. The lowest (2-5 ng/ml) vs. highest (6-9 ng/ml) scores for this post-HFM leptin measurement identified distinct OR and OP subgroups, respectively, when they were similar in body weight (340-350 g), premeal leptin (2.6-3.4 ng/ml), and meal size (40 kcal). Subsequent tests in these normal-weight OP rats revealed a distinct characteristic compared with OR rats, namely, exaggerated HFM-induced rise in expression of the orexigenic peptide galanin in the paraventricular nucleus. Thus, with this HFM-induced leptin measurement, OP rats can be identified while still at normal weight and then investigated for mechanisms that contribute to their excessive body fat accrual on a high-fat diet.     

Energy balance and facultative diet-induced thermogenesis in mice fed a high-fat diet

The present study was aimed at studying energy balance in mice fed a high-fat diet. Albino mice were divided into three groups. One group had free access to the stock diet, whereas the two other groups consumed a high-fat diet. One of the high-fat fed groups was fed ad libitum, whereas the other was offered a restricted amount of the same diet so that its energy intake was comparable to the group of mice given the stock diet. Energy balance measurements, which included indirect calorimetry and carcass analysis, were performed. Brown adipose tissue (BAT) properties were also investigated. The results show that gains in both body weight and fat were higher in mice that had free access to high-fat diet than in mice fed the stock diet. In animals given a restricted amount of the high-fat diet, fat gain increased, whereas protein gain was reduced in comparison with animals fed the stock diet. Unrestricted access to the high-fat diet led to an increase in both energy intake and energy gain. As revealed by both slaughter and indirect calorimetry techniques energy expenditure was, in high-fat fed mice, 40% higher than in animals fed either stock or a restricted amount of high-fat diet. Nadolol was shown to suppress a large part of the elevated metabolic rate seen in mice fed an unrestricted high-fat diet. In those mice, BAT mitochondrial GDP binding was also increased. In summary, the present results confirm that adaptive diet-induced thermogenesis (DIT) develops in mice made hyperphagic by an energy-dense palatable diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inflammatory response to a high-fat, low-carbohydrate weight loss diet: effect of antioxidants

The objective of this study was to test the hypothesis that the inflammatory response to a high-fat, low-carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI>27 kg/m(2)) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre- and post serum samples were measured for markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8-epi-prostaglandin-F(2alpha) (8-epi)). HF resulted in significant reductions in weight (-3.2%), glucose (-18.7%), and MCP-1 (-15%) (all P<0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P=0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r= -0.501), 8-epi (r= -0.863), and ORAC (r= -0.546) (all P<0.05). It was concluded that weight loss on a short-term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet-controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.     

Body composition assessment in extreme obesity and after massive weight loss induced by gastric bypass surgery

Body composition methods were examined in 20 women [body mass index (BMI) 48.7 +/- 8.8 kg/m(2)] before and after weight loss [-44.8 +/- 14.6 (SD) kg] after gastric bypass (GBP) surgery. The reference method, a three-compartment (3C) model using body density by air displacement plethysmography and total body water (TBW) by H(2)18O dilution (3C-H(2)18O), showed a decrease in percent body fat (%BF) from 51.4 to 34.6%. Fat-free mass hydration was significantly higher than the reference value (0.738) in extreme obesity (0.756; P < 0.001) but not after weight reduction (0.747; P = 0.16). %BF by H(2)18O dilution and air displacement plethysmography differed significantly from %BF by 3C-H(2)18O in extreme obesity (P < 0.05) and 3C models using (2)H(2)O or bioelectrical impedance analysis (BIA) to determine TBW improved mean %BF estimates over most other methods at both time points. BIA results varied with the equation used, but BIA better predicted %BF than did BMI at both time points. All methods except BIA using the Segal equation were comparable to the reference method for determining changes over time. A simple 3C model utilizing air displacement plethysmography and BIA is useful for clinical evaluation in this population.     

Cinnamon extract prevents the insulin resistance induced by a high-fructose diet.

The aim of this study was to determine whether cinnamon extract (CE) would improve the glucose utilization in normal male Wistar rats fed a high-fructose diet (HFD) for three weeks with or without CE added to the drinking water (300 mg/kg/day). In vivo glucose utilization was measured by the euglycemic clamp technique. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle were performed afterwards by Western blotting. At 3 mU/kg/min insulin infusions, the decreased glucose infusion rate (GIR) in HFD-fed rats (60 % of controls, p < 0.01) was improved by CE administration to the same level of controls (normal chow diet) and the improving effect of CE on the GIR of HFD-fed rats was blocked by approximately 50 % by N-monometyl-L-arginine. The same tendency was found during the 30 mU/kg/min insulin infusions. There were no differences in skeletal muscle insulin receptor (IR)-beta, IR substrate (IRS)-1, or phosphatidylinositol (PI) 3-kinase protein content in any groups. However, the muscular insulin-stimulated IR-beta and IRS-1 tyrosine phosphorylation levels and IRS-1 associated with PI 3-kinase in HFD-fed rats were only 70 +/- 9 %, 76 +/- 5 %, and 72 +/- 6 % of controls (p < 0.05), respectively, and these decreases were significantly improved by CE treatment. These results suggest that early CE administration to HFD-fed rats would prevent the development of insulin resistance at least in part by enhancing insulin signaling and possibly via the NO pathway in skeletal muscle.     

Explanations for weight loss after ileojejunal bypass in gross obesity.

Twenty grossly obese patients underwent ileojejunal bypass operations. Measurements of calories lost in faeces showed that the malabsorption could not account for the weight loss. Furthermore, the malabsorption was not decreased two years after bypass, when weight was no longer being lost. Dietary restriction is therefore largely responsible for the weight loss and increased food intake for weight maintenance.