Weihong Sun

Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway.

Publisher: Wiley

Date: 11-01-2016

DOI: 10.1111/HEPR.12634

Abstract: Overwhelming oxidative stress is implicated as crucial in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Liraglutide, a well-established antidiabetes drug, was recently reported to ameliorate NAFLD with an elusive mechanism. We used a mouse model to examine whether liraglutide could ameliorate NAFLD and explored the possible mechanisms. Twenty C57BL/6J mice were randomly treated with a normal-fat diet or high-fat diet for 16 weeks, then further distributed into four groups and subjected to s.c. injection of liraglutide or saline for 4 weeks. The growth/metabolism, oxidative stress, mitochondrial architecture and autophagy were assessed prospectively at the 20th week. High-fat diet inducement resulted in severe NAFLD while liraglutide treatment significantly reversed the trend, marked by reduced bodyweight, improved glucose tolerance and liver triglyceride composition. Reduced hepatic malondialdehyde level, increased mRNA and protein levels of CATALASE and MNSOD indicated liraglutide affected both the oxidative and antioxidative process to ameliorate oxidative stress. After liraglutide administration, the upregulated mRNA and protein levels of mitochondrial fission and fusion-related DRP1, OPA1 and respiratory chain-related COMPLEX1, UCP2 demonstrated the enhancement of mitochondrial architecture which may attenuate the generation of reactive oxygen species (ROS), while the diminished mRNA and protein level of P62 and increased levels of Beclin1 and LC3II/I ratio indicated the promoting autophagy, which probably contribute to the ROS elimination. Further, restored protein levels of Sirtuin1/Sirtuin3 and the downstream p-FOXO3a reveal the probable pathways of liraglutide acting on autophagy. Liraglutide diminishes oxidative stress by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a-LC3 pathway to ameliorate diet-induced NAFLD.

Effects of High Blood Pressure on Cardiovascular Disease Events Among Chinese Adults With Different Glucose Metabolism.

Publisher: American Diabetes Association

Date: 12-07-2018

DOI: 10.2337/DC18-0918

Abstract: To investigate cardiovascular disease (CVD) risks caused by blood pressure (BP) of 130-139/80-89 mmHg among Chinese adults with different glucose metabolism. A prospective population-based cohort of 2,132 adults in Shanghai was established in 2002, and CVD information was collected during 10.9 years of follow-up. After assessing the association between BP categories and incident CVD, we analyzed the risk for CVD by blood glucose categories and BP categories combined by using multiple Cox regression analysis among 1,419 participants at follow-up. The corresponding incidence of CVD per 1,000 person-years for the BP <130/80 mmHg, 130-139/80-89 mmHg, and ≥140/90 mmHg or treated groups were 3.0, 6.0, and 13.9, respectively. After adjusting for age, sex, and other factors, BP ≥140/90 mmHg was significantly associated with a higher CVD risk in general (hazard ratio 2.68 [95% CI 1.36-5.25]) and in various blood glucose categories (normoglycemia 2.59, prediabetes 3.03, diabetes mellitus [DM] 4.98). However, BP of 130-139/80-89 mmHg was significantly associated with a higher CVD risk in an estimated baseline 10-year atherosclerotic CVD (ASCVD) risk ≥10% (3.82 [1.42-9.78]) or DM (3.54 [1.05-11.88]) but not in the general population or for a baseline 10-year ASCVD risk <10%, normoglycemia, or prediabetes. BP of 130-139/80-89 mmHg may result in a significantly higher CVD risk in Chinese adults with an estimated 10-year ASCVD risk ≥10% or DM but not in those with normoglycemia or prediabetes.

University Of Tsukuba

Location: Japan

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Shanghai Institute Of Nutrition And Health, Chinese Academy Of Sciences

Location: China

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Shanghai Institutes For Biological Sciences, Chinese Academy Of Sciences

Location: No location found

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Shanghai Institutes For Biological Sciences, Chinese Academy Of Sciences

Location: China

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