Relationship between ghrelin and energy expenditure in healthy young women

Ghrelin is a novel peptide that has been isolated from human and rat stomach tissues. Despite its known stimulatory effects on appetite and eating behavior, little information is available regarding its relationship with energy expenditure in normal-weight humans. To address this issue, we examined the relationship between serum ghrelin and resting metabolic rate (RMR), the thermic effect of food (TEF), fasting and postprandial respiratory quotient, physical activity level, peak aerobic capacity (VO(2 peak)), energy intake, and psychological measures of feeding behavior. We recruited 65 young healthy women and determined RMR and TEF by indirect calorimetry after a 12-h fast. Physical activity was determined by a leisure time physical activity questionnaire; VO(2 peak) was determined by bicycle ergometer test to exhaustion; energy intake was determined by a 24-h dietary recall; and food behavior was determined by a three-factor eating questionnaire. Our cohort showed a broad range of body mass index (range, 16.8-28.3 kg/m2), RMR (range, 820-1550 kcal/d), TEF (range, 74.4-136.5 kcal/d), and percent body fat (range, 14.0-37.7%). We noted significant inverse correlations between ghrelin and RMR (r = -0.350, P = 0.004) and TEF (r = -0.396, P = 0.001). These inverse correlations persisted after statistical control for both fat-free mass and fat mass (ghrelin vs. RMR partial, r = -0.284, P = 0.024; and ghrelin vs. TEF partial, r = -0.329, P = 0.01) and insulin levels (ghrelin vs. RMR partial, r = -0.255, P = 0.046; and ghrelin vs. TEF partial, r = -0.287, P = 0.024) using partial correlation analysis. We also observed a significant inverse correlation between ghrelin and daily caloric intake (r = -0.266, P = 0.032), but ghrelin levels were not significantly correlated with fasting (r = -0.002), postprandial respiratory quotient (r = -0.016), leisure time physical activity (r = 0.104), VO(2 peak) (r = 0.138), dietary disinhibition (r = -0.071), dietary restraint (r = 0.051), or feeling of general hunger (r = -0.028). These results suggest that higher levels of ghrelin are associated with low levels of resting and postprandial thermogenesis, which is independent of individual differences in fat-free mass and fat mass. Although speculative, serum ghrelin may play a role in the regulation of energy homeostasis by acting as a hormonal marker of increased energy efficiency.     

Acute and Chronic Effects of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Visfatin and Apelin Levels in Patients with Severe Obesity

Background

Visfatin is an adipokine linked to obesity and inflammation, and it has insulin-mimetic properties. Apelin is an adipokine with positive cardiac inotropic effects, and it may be related to inflammatory molecules. Variations in plasma visfatin and apelin levels following bariatric surgery remain controversial.

Methods

In this study, patients who underwent a biliopancreatic diversion with duodenal switch (BPD-DS) were compared to a severely obese group (control group). Anthropometric measures and blood samples were taken before surgery, on days 1 and 5, as well as at 6 and 12 months after surgery in the BDP-DS group. For the control group, the tests were performed at baseline and at 6 and 12 months.

Results

Seventy subjects in the BPD-DS group and 28 in the control group were included. The expected reduction in body weight at 1 year after a BPD-DS was observed (85.9?±?18.5 vs. 136.6?±?27.7 kg at baseline; p?<?0.001). Plasma visfatin levels decreased at day 1 (16.13?±?5.56 vs. 18.82?±?7.36 ng/mL at baseline; p?=?0.001), while plasma apelin levels decreased at day 5 (0.50?±?0.28 vs. 0.55?±?0.33 ng/mL at baseline; p?=?0.040) after surgery. There were no changes at 6 and 12 months compared to baseline, and no changes were observed in the control group.

Conclusions

Our data show that 1-year weight loss induced by BPD-DS did not influence the overall plasma visfatin and apelin levels in severely obese patients.     

Changes in predicted cardiovascular disease risk after biliopancreatic diversion surgery in severely obese patients

Objective

To determine the impact of biliopancreatic diversion with duodenal switch (BPD-DS) surgery on cardiovascular risk profile and predicted cardiovascular risk in severely obese patients.

Materials/Methods

We compared 1-year follow-up anthropometric and metabolic profiles in severely obese who underwent BPD-DS (n = 73) with controls (severely obese without surgery) (n = 33). The 10-year predicted risk for coronary heart disease (CHD) was estimated using the Framingham risk-tool. We assigned 10-year and lifetime predicted risks to stratify subjects into 3 groups: 1) high short-term predicted risk (≥ 10% 10-year risk or diagnosed diabetes), 2) low short-term (< 10% 10-year risk)/low lifetime predicted risk or 3) low short-term/high lifetime predicted risk.

Results

During the follow-up period, body weight and body mass index decreased markedly in the surgical group (− 52.1 ± 1.9 kg and − 19.0 ± 0.6 kg/m² respectively, p < 0.001) vs. (− 0.7 ± 1.0 kg and − 0.3 ± 0.4 kg/m², p = 0.51). Weight loss in the surgical group was associated with a reduction in HbA_1C (6.2% vs. 5.1%), HOMA-IR (61.5 vs. 9.3), all lipoprotein levels, as well as blood pressure (p < 0.001). The 10-year CHD predicted risk decreased by 43% in women and 33% in men, whereas the estimated CHD risk in the non surgical group did not change. Before surgery, none of the women and only 18% of men showed low short-term/low lifetime predicted risk, whereas a significant proportion of subjects had high short-term predicted risk (36% in women and 12% in men). Following surgery, 52% of women and 55% of men have a low short-term/low lifetime predicted risk.

Conclusions

These results highlight the cardiovascular benefits of BPD-DS and suggest a positive impact on predicted CHD risk in severely obese patients. Long-term studies are needed to confirm our results and to ascertain the effects on CHD risk estimates after BPD-DS surgery.     

促酰化蛋白受体C5L2在前脂肪细胞分化过程和脂肪酸负荷下的表达研究

目的 观察3T3-L1前脂细胞分化和游离脂肪酸（FFA）对3T3-L1（前）脂肪细胞C5L2基因和蛋白表达的影响。方法采用逆转录（RT）-PCR和流式细胞仪检测不同分化时段和FFA处理后（前）脂肪细胞C5L2mRNA和蛋白表达。结果 3T3-L1脂肪细胞C512mRNA表达呈分化依赖性增加,而C5L2蛋白表达水平在分化早期显著增强,诱导分化6hC5L2蛋白表达增加了21％（61％±18％VS51％±15％,P〈0．05）;分化12h达高峰,增加了38％（70％±12％VS51％±15％,P〈0．01）;分化3d基本恢复至0d水平。在3T3-L1成熟脂肪细胞,0．5mmol／L和1．0mmol／L油酸分别抑制46％（0．58±0．21 vs 1．08±0．46,P〈0．05）和84％（0．18±0．04VS1．08±0．46,P〈0．05）C5L2 mRNA表达,而0．125mmol／L油酸即能显著下调36％（35％±8％vs54％±7％,P〈0．01）C5L2蛋白表达。低浓度棕榈酸均能明显抑制C5L2mRNA和蛋白的表达,1．0mmol／L时c512mRNA和蛋白表达分别减少了41％（0．57±0．28vs0．97±0．41,P〈0．05）和55％（24％±13％VS54％±7％,P〈0．01）。油酸和棕榈酸对前脂肪细胞C512表达差异无统计学意义。结论促酰化蛋白／C5L2途径参与了脂肪细胞分化的调控过程。C512mRNA和蛋白表达的下调可能参与了油酸和棕榈酸诱导的成熟脂肪细胞胰岛素抵抗的发生。     

Novel adipokines: links between obesity and atherosclerosis

Today, cardiovascular diseases (CVD) remain the principal cause of death in industrialized countries and are linked to obesity and metabolic syndrome. Metabolic syndrome is characterized by changes in arterial blood pressure, glucose metabolism, lipid and lipoprotein profiles in addition to inflammation. Adipose tissue produces many cytokines and secretory factors termed adipokines. Intra-abdominal (visceral) adipose tissue in particular, rather than peripheral, appears to be associated with global cardiometabolic risk. The present article summarizes information on five recently discovered adipokines: vaspin, visfatin, apelin, acylation stimulating protein (ASP) and retinol-binding protein 4 (RBP4) and their potential beneficial or deleterious roles in obesity and atherosclerosis. Vaspin may have antiatherogenic effects through its potential insulin-sensitizing properties. Similarly, visfatin has been suggested to enhance insulin sensitivity, but its potential role in plaque destabilization may counteract this. Apelin, via inhibition of food intake, and increases in physical activity and body temperature, may promote weight loss, resulting in a beneficial antiatherogenic effect. Further, favourable effects on vasodilatation and blood pressure add to this positive effect. Considering its increased levels in subjects with demonstrated atherosclerosis, RBP4 may constitute a biomarker. Lastly, ASP, often increased in obesity and metabolic disorders, may be contributing to efficient lipid storage, and decreasing or blocking ASP may provide a potential antiobesity target. Adipokines may further contribute to obesity-atherosclerosis relationships, the full understanding of which will require further research.     

The therapeutic role of very low-density lipoprotein receptor gene in hyperlipidemia in type 2 diabetic rats

Hyperlipidemia is a common feature of type 2 diabetes and is related to cardiovascular disease. The very low-density lipoprotein receptor (VLDLR) binds to and internalizes triglyceride-rich lipoproteins with high specificity. In this study, we evaluated the role of VLDLR in hyperlipidemia in type 2 diabetic rats. Type 2 diabetes was induced in male Wistar rats by injection of low-dose streptozotocin coupled with a high-fat diet. Recombinant adeno-associated viral (rAAV) vectors encoding the human VLDLR gene (rAAV·VLDLR) were intravenously administered to diabetic rats. Results showed that in vivo, total VLDLR mRNA and protein levels were significantly decreased in skeletal muscle (type I VLDLR mainly reduced) and adipose tissue (type II VLDLR mainly reduced) but not in heart in hypercholesterolemic, hypertriglyceridemic diabetic rats compared with normal rats. And in vitro, in 3T3-L1 adipocytes, insulin-induced (1.0?mmol/liter) insulin resistance significantly decreased VLDLR mRNA expression. In rats, rAAV·VLDLR delivery resulted in a reduction in serum cholesterol and triglyceride that lasted for the duration of the study (12 weeks). Fasting blood insulin was significantly lower in the rAAV·VLDLR group versus untreated diabetic rats although fasting blood glucose levels were not significantly different in both groups at the end of the study. rAAV·VLDLR-treated animals had significantly increased lipoprotein lipase activity and reduced aortic atherosclerosis. Taken together, our data suggest that type 2 diabetes and related insulin resistance manifest decreased VLDLR with elevated serum cholesterol and triglyceride levels, and overexpression of VLDLR through a single injection of rAAV·VLDLR reversed these effects and consequentially attenuated aorta atherosclerotic plaque progression.     

诱导SW872前脂肪细胞分化的最优方法探讨

目的探讨诱导SW872脂肪细胞分化的最优方法。方法根据不同的分化诱导刺激分为6组:①对照组:无分化刺激,仅有DMEM/F12培养基;②胰岛素组:含2 mg/L Insulin;③1-甲基3-异丁基黄嘌呤组:含0.5 mmol/L IBMX;④促酰化蛋白组:含50 mg/L ASP;⑤激素鸡尾酒(胰岛素 1-甲基3-异丁基黄嘌呤 地塞米松组:含2 mg/L insulin 0.5 mmol/L IBMX 1.0μmol/L DEX;⑥油酸(oleic acid)组:含0.2 mg/L oleic acid。通过形态学观察、油红染色、测定细胞甘油三酯总量的方法。结果多组分化刺激中,油酸组刺激可在24 h内诱导SW872细胞分化,而且分化均匀,分化率高,分化后形成的脂肪细胞形态典型;而且油酸组促进SW872细胞分化过程中细胞内甘油三酯的积累。结论油酸是诱导SW872细胞分化的最佳方法,该方法的建立和统一,为进一步利用SW872细胞进行脂代谢、脂肪细胞功能的研究奠定了基础。