Objective To analyze the glucolipotoxicity effects of glucose combined with free fatty acid (FFA) on ketone production and ultrastructure of skeletal muscle, by exogenous elevating circulating glucose and FFA concentration. Methods Fifty Wistar rats were divided into high-fat-feed induced obesity group (OB group, n=40) and ordinary feed as normal control group (NC group, n=10). Circulating glucose and FFA levels were increased by infusion in high-fat-fed obese rats. The levels of serum lipid, plasma FFA and beta-hydroxybutyric acid were detected by the horizontal colorimetry, and the microstructure of skeletal muscle was observed by transmission electron microscopy, especially the changes of the mitochondrial structure. Euglycemic-hyperinsulinemic clamp with tracer infusion was performed to assess peripheral insulin sensitivity. Results The average weight and body fat ratio in the OB group was higher than that in the NC group (P<0.05). Insulin clamp test to assess peripheral insulin sensitivity showed that the steady-state glucose Infusion rate in the OB group during clamp test was significantly lower than that in the NC group [OB: (19.26±1.84) mg/(kg·min)vs. NC: (28.82±1.69) mg/(kg·min), P<0.05]. The mitochondrial denaturation of skeletal muscle in the OB group of rats was observed, and the swelling and crest permutation, the accumulation of lipid droplets and cavitation were formed, and hypertrophy of mitochondria were also seen after intralipid and glucose infusion, which was obvious in the combined infusion group. Conclusions By exogenous elevating circulating glucose and FFA concentration, the products of ketone body increases. The mitochondrial damage of skeletal muscle suggests that mitochondrial may be the potential target of glucoxicity and lipotocicity.
ObjectivesTo systematically review the efficacy and safety of Orlistat for obese patients with cardiovascular risk including hyperlipidemia, hypertension, diabetes and prediabetes.MethodsSinomed, CNKI, WanFang Data, PubMed, EMbase, The Cochrane Library and ClinicalTrails.gov databases were electronically searched to collect randomized controlled trials (RCTs) of Orlistat for obese patients with cardiovascular risk such as hyperlipemia, diabetes, prediabetes and hypertension from inception to Jan 7th, 2017. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using Stata 14.0 software.ResultsA total of 28 RCTs were included. The results of meta-analysis showed that, compared with placebo, Orlistat could significantly reduce the weight (MD=–2.85, 95%CI –3.47 to –2.24, P=0.000), waist (MD=–2.45, 95%CI –3.07 to –1.83, P=0.000) and BMI (MD=–1.29, 95%CI –2.08 to –0.49, P=0.002) of patients. Orlistat could also control the blood pressure, blood glucose and other cardiovascular risk factors well. Compared with the blank control, Orlistat could improve the waist and parts of cardiovascular risk factors (P<0.05). The incidence of adverse events of Orlistat was slightly higher than that of placebo, but most could be self-healing.ConclusionsCurrent evidence shows that compared with placebo and blank control, Orlistat is effective for improving both weight loss and some cardiovascular risk factors. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
ObjectiveTo systematically review the efficacy and safety of orlistat in the treatment of overweight and obese type 2 diabetes mellitus (T2DM). Methods PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of orlistat in the treatment of overweight and obese T2DM patients from inception to June 29th, 2022. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies; then, meta-analysis was performed by using Stata 16.0 software. Results A total of 24 RCTs involving 3 702 patients were included. The results of meta-analysis showed that compared with control group, orlistat group could significantly decrease the levels of fasting blood glucose (WMD=1.04, 95%CI 0.80 to 1.29, P<0.001), 2h postprandial blood glucose (WMD=1.17, 95%CI 0.78 to 1.56, P<0.001) and hemoglobin A1c (WMD=0.84, 95%CI 0.51 to 1.17, P<0.001), and the levels of total cholesterol, triglyceride, low density lipoprotein, body weight and body mass index also significantly decreased (P<0.001). The incidence of adverse events such as increased defecation and abdominal pain of orlistat was slightly higher than that of control group; however, most could be self-healing.Conclusion Current evidence shows that orlistat can effectively and safely improve blood sugar, lipid index in overweight and obese T2DM patients. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.