Obesity-induced testicular oxidative stress,inflammation and apoptosis: Protective and therapeutic effects of orlistat

Obesity has been reported to induce oxidative stress, inflammation and apoptosis in the testis. The objective of this study was to determine the effects of the anti-obesity drug orlistat, on testicular oxidative stress, inflammation and apoptosis in high-fat diet (HFD)-fed rats. Twenty-four adult male Sprague Dawley rats weighing 250−300 g were randomized into four groups (n = 6/group), namely; normal control (NC), high-fat diet (HFD), HFD plus orlistat (10 mg/kg body weight/day administered concurrently for 12 weeks) (HFD + Opr) and HFD plus orlistat (10 mg/kg body weight/day administered 6 weeks after induction of obesity) (HFD + Ot) groups. Antioxidant enzymes activities were significantly decreased, while mRNA levels of pro-apoptotic markers (p53, Bax/BCl-2, caspase-9, caspase-8 and caspase-3) were significantly increased in the testis of HFD group relative to NC group. Furthermore, the mRNA levels of pro-inflammatory markers (nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis factor alpha and interleukin (IL)-1β increased significantly, while anti-inflammatory marker (IL-10) decreased significantly in the testis of the HFD group relative to NC group. However, in both models of orlistat intervention (protective and treatment models) up-regulated antioxidant enzymes, down-regulated inflammation and apoptosis were observed in the testis of HFD-fed rats. Orlistat ameliorated testicular dysfunction by attenuating oxidative stress, inflammation and apoptosis in HFD-fed rats, suggesting its potential protective and therapeutic effects in the testis compromised by obesity.     

六君子汤加味联合奥利司他治疗脾虚湿阻证单纯性肥胖症临床研究

目的:观察六君子汤加味联合奥利司他治疗脾虚湿阻证单纯性肥胖症的临床疗效及对血清瘦素(leptin)和脂联素(ADPN)水平的调节作用。方法:将80例患者随机分为对照组40例和观察组40例,对照组口服奥利司他治疗,观察组在对照组的基础上加用六君子汤加味治疗,2组均连续治疗12周;观察比较2组脾虚湿阻证证候评分、肥胖指征、临床疗效及血清leptin、ADPN水平。结果:总有效率观察组为95.00%,对照组为75.00%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组患者浮肿、疲乏无力、肢体困重、纳差、腹满等脾虚湿阻证证候评分较治疗前明显下降(P<0.05),且观察组上述各项评分均低于对照组(P<0.05)。治疗后,2组患者体质量、体质量指数(BMI)、体脂含量(FAT)值均较治疗前明显下降(P<0.05),且观察组上述各指标改善较对照组更显著(P<0.05)。治疗后,2组血清leptin水平均较治疗前降低(P<0.05),ADPN水平升高(P<0.05);且观察组两项指标改善较对照组更显著(P<0.05)。结论:六君子汤加味联合联合奥利司他治疗脾虚湿阻证单纯性肥胖症疗效显著,调节leptin、ADPN水平可能是其作用机制之一。     

A Comparison of Meal Replacements and Medication in Weight Maintenance after Weight Loss

Objective: To compare the use of meal replacements or medication during weight maintenance subsequent to weight loss using a very low-energy diet (VLED) in overweight or obese adults.

Design: Participants followed a liquid VLED of 2177 kJ for 12 weeks followed by 4 weeks of re-orientation to solid foods. Participants were randomized at week 16 to receive either meal replacements or Orlistat both combined with a structured meal plan containing an energy value calculated to maintain weight loss.

Subjects: Sixty-four women (age = 49.9 ± 10 y, weight = 101.6 ± 17.1 kg, height = 164.9 ± 6.0 cm, BMI = 36.7 ± 5.4 kg/m²) and 28 men (age = 53.7 ± 9.6 y, weight = 121.8 ± 16.0 kg, height = 178.7 ± 5.6 cm, BMI = 37.8 ± 4.9 kg/m²) completed a 1 year weight management program. Behavioral weight management clinics included topics on lifestyle, physical activity (PA), and nutrition. Participants met for 90 min weekly for 26 weeks, and then biweekly for the remaining 26 weeks.

Outcomes: Minutes of PA, fruits and vegetables (FV), and pedometer steps were recorded on a daily basis and reported at each group meeting. Body weight was obtained at each group meeting.

Results: During VLED, the MR group decreased body weight by 22.8 ± 6.1 kg and the Orlistat group decreased body weight by 22.3 ± 6.1 kg. During weight maintenance, there was no significant group by time interaction for body weight, PA, FV consumption, or pedometer steps. At week 16, the meal replacement group had a body weight of 85.4 ± 14.3 kg that increased to 88.1 ± 16.5 kg at 52 weeks (p < 0.05). At week 16, the Orlistat group had a body weight of 85.7 ± 17.9 kg that increased to 88.5 ± 20.3 kg at 52 weeks (p < 0.05).

Conclusions: Subsequent to weight loss from a VLED, meal replacements and Orlistat treatments were both effective in maintaining weight significantly below baseline levels over a 52 week period of time. Meal replacements may be a viable alternative strategy to medications for weight maintenance.     

奥利司他结合低热量饮食治疗肥胖伴非酒精性脂肪性肝病的临床研究

目的　评价奥利司他结合低热卡饮食在治疗肥胖伴非酒精性脂肪性肝病 (NAFLD)中的作用。方法　选择体重指数 (BMI)在 2 7和 4 0之间 ,伴有肝功能异常的NAFLD患者 6 0例 ,给予奥利司他 12 0mg ,每日 3次 ,进食时服用 ,结合低热卡饮食 ,共治疗 2 4周。 结果　①治疗后所有患者的体重和BMI均有下降 ,下降率均达治疗前的 (10 .76± 4 .5 2 ) %。②治疗 12周后常规肝功能中天冬氨酸转氨酶(AST)、丙氨酸转氨酶 (ALT)、γ 谷氨酰转肽酶 (GGT)及总胆红素与治疗前比较有显著改善 ,并维持至整个 2 4周 (P值均 <0 .0 5 )。③治疗后肝CT密度值 [分别为 (37.2 9± 13.17)Hu和 (49.2 0± 12 .2 4 )Hu]及肝 /脾密度比值 (分别为 0 .70± 0 .2 3和 0 .94± 0 .2 5 )均显著增加 (P值均 <0 .0 1)。④ 5 8例中 5 0例(86 .2 % )肝功能改善 ,其中 4 7例 (94 % )同时伴有CT肝 /脾密度比值的增加 ,8例治疗后肝功能未改善 ,但其中 5例肝 /脾CT密度比值增加 ;5 2例 (90 % )肝 /脾CT密度比值较治疗前增加 ,且其中 4 1.4 %患者肝 /脾CT密度比值增至≥ 1,仅 6例肝 /脾CT密度比值下降 ,然而其中仍有 3例肝功能有改善。⑤高胆固醇血症和高三酰甘油血症患者 ,治疗前后也有显著改善 (治疗前分别为 36 .6 7%和 6 1.6 7% ,治疗后分别为 2 3.     

Effects of sibutramine and orlistat on mood in obese and overweight subjects: a randomised study

Background and aimIntentional weight loss results in improvement in mood. Very few data exist regarding the effects of sibutramine on the mood of obese and overweight patients in general clinical samples. Moreover, no study has evaluated the effects of orlistat treatment on mood. The purpose of our study was to assess the effects of sibutramine and orlistat on mood in obese and overweight subjects.Methods and resultsSixty obese and overweight women were divided into three groups. The first group (n = 20) received a low-calorie diet and sibutramine 10 mg; the second group (n = 20) received a low-calorie diet and orlistat 120 mg three times a day, and the third group received only the low-calorie diet.ConclusionA psychiatric assessment was performed with the Hamilton Depression Rating Scale (HAMD) before and after 3 months of treatment. In all the groups a statistically significant decrease in HAMD scores was observed. However, the decrease in the sibutramine group was greater compared to that observed in the two other groups (P < 0.01). These results suggest that sibutramine treatment may improve mood more than diet alone or orlistat therapy in a general clinical sample of obese patients.     

肥胖伴非酒精性脂肪性肝病的临床研究

目的　探讨非酒精性脂肪性肝病 (NAFLD)的发病机制及奥利司他结合低热量饮食治疗对NAFLD的有效性和安全性。方法　将 10 7例病人分为 4组。A组为肥胖伴NAFLD和肝损伤组 (60例 ) ,B组为无脂肪肝肥胖组 (16例 ) ,C组为肥胖伴NAFLD组 (12例 ) ,D组为丙氨酸转氨酶 (ALT)和天冬氨酸转氨酶 (AST)均升高组 (19例 ) ,其中A组给予奥利司他 12 0mg ,每日 3次 ,结合低热卡饮食 ,共治疗 2 4周。分别检测各组相关代谢指标。结果　①各组之间胰岛素 (INS)、瘦素、游离脂肪酸 (FFA)、铁蛋白、胰岛素抵抗指数 (IR)水平差异无显著性 ,而转化生长因子 (TGF) β1在A组与C组和C组与D组间差异有显著性 (P =0 .0 0 0 3 0 )。②TGF β1和FFA与肝 /脾比值 (LSR )呈负相关 ,AST、谷氨酰转肽酶 (GGT)与LSR呈负相关 ,白细胞与LSR呈正相关。③A组病人在治疗 2 4周后体重指数 (BMI)下降达 10 .76%±4.5 2 %。AST、ALT、GGT及总胆红素有显著改善 ,治疗后LSR亦显著增加 (P <0 .0 1)。④不良作用发生率为 96.7% ,均与排便有关。结论　奥利司他结合低热量饮食可改善肝功能和相关代谢综合征 ,可作为肥胖伴NAFLD的药物治疗选择     

Role of ezetimibe in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.     

Inhibitory Effects of Corni Fructus Extract on Angiogenesis and Adipogenesis

Natural products in Chonnam, Korea were screened via anti-angiogenesis experiments, and 1 candidate product was identified, Corni fructus, which exerted dose-dependent inhibitory effects against angiogenesis, adipogenesis, and cell adhesion. C. fructus extract (CFE) exhibits an angiogenesis inhibitory effect superior to that of the EGCG from green tea leaves. The expression level of angiogenesis and adipogenesis-related signal molecules in the western blotting was reduced by increasing the amount of added CFE. Moreover, a diet supplemented with CFE was deemed more effective in inducing weight loss in LB mice than a representative synthetic diet drug, orlistat, which incidently caused the side effect of denuding the mice of their hair. These results indicate that C. fructus may prove to be a useful anti-adipogenic compound, and these in vitro results may be reflected later under in vivo conditions.     

Adherence, behavior change, and visualization: a qualitative study of the experiences of taking an obesity medication

OBJECTIVE: Our objective was to examine patients' experiences of taking orlistat as a means to explore adherence and behavior change. METHOD: We performed qualitative interviews with 12 participants who had taken orlistat in the past 2 years. RESULTS: Their experiences were described in terms of beliefs about the causes of their obesity, their motivations for taking orlistat, and highly visual side effects. These themes have implications for understanding adherence and behavior change. For some, the side effects led to nonadherence and absence of behavior change. These individuals seemed to be motivated by routine effects of being overweight, such as lowered self-esteem. In contrast, those who were motivated by a life crisis seemed to tolerate the side effects of the drug, leading to adherence. In turn, these highly visual side effects enabled them to make an explicit link between food consumed and weight, creating a shift in their beliefs about the causes of obesity and making behavior change more likely. CONCLUSION: Orlistat use illustrates how treatment and illness beliefs interact to create both adherence and behavior change, particularly in the context of a life crisis and particularly when symptoms can be visualized.