Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis

ABSTRACT Objective Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk. Materials and methods The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis. Results A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72). Conclusions Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.

Resveratrol suppresses hyperglycemia-induced activation of NF-κB and AP-1 via c-Jun and RelA gene regulation.

Background: Resveratrol (RSV) provides several important biological functions in wide variety of cells. In this study, we investigated the molecular mechanisms underlying anti-inflammatory effect of RSV on HepG2 cells by assessing the gene expression of RelA and c-Jun- subunits of NF-κB and AP-1 transcription factors. Methods: HepG2 cells were settled in a serum- free medium with high concentrations of glucose (30 mM) and insulin (1 µM) overnight and were then incubated with RSV (5, 10, and 20 µM) for 24 and 48 hours. Real time quantitative polymerase chain reaction (qRT-PCR) was used to determine RelA and c-Jun expression. Results: RSV diminished hyperglycemia/hyperinsulinemia stimulated expression of c-Jun dose- dependently after 24 and 48 hours (p<0.05). In addition, RelA gene expression was decreased dose-dependently in all RSV doses after 48-hour incubation (p<0.05). Our results indicated that RSV may reduce NF-κB and AP-1 activity via RelA and c-Jun gene regulation. Conclusion: The findings of the present study demonstrated that RSV may be considered as a preventative and therapeutic agent for antagonizing inflammation in Hepatocellular carcinoma (HCC).

Does Resveratrol Improve Insulin Signalling in HepG2 Cells?

OBJECTIVES: Diabetes mellitus is a common metabolic disorder with high global prevalence. It is characterized by a decrease in insulin secretion or a decrease in insulin sensitivity or both. The aim of the present study was to investigate the effects of resveratrol treatment on the expression of the genes involved in insulin signalling cascade, such as Forkhead box protein O1 (FoxO1), 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and mammalian target of rapamycin (mTOR). METHODS: HepG2 cells were cultured in serum-free medium with high concentrations of glucose and insulin and then were treated with resveratrol (5, 10 and 20 µM) for 24 and 48 hours. Complementary deoxyribonucleic acids (cDNAs) were synthesized followed by RNA extraction. Real-time quantitative reverse transcription polymerase chain reaction was used to analyze the expression of FoxO1, PDPK1 and mTOR. RESULTS: Resveratrol increased the expression of PDPK1, mTOR and FoxO1. No significant difference was seen among differing dosages of resveratrol, but treatments for 48 hours exerted the greatest effectiveness. CONCLUSIONS: Our results were consistent with other studies showing the beneficial effects of resveratrol on diabetes. However, considering the effects of resveratrol in increasing FoxO1 and gluconeogenic gene expression, long-term usage of resveratrol should be investigated in greater depth in future studies.