AMP-activated protein kinase is a key regulator of obesity-associated factors.

An imbalance between caloric intake and energy expenditure leads to obesity. Obesity is an important risk factor for the development of several metabolic diseases including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. So, controlling obesity could be effective in the improvement of obesity-related diseases. Various factors are involved in obesity, such as AMP-activated protein kinases (AMPK), silent information regulators, inflammatory mediators, oxidative stress parameters, gastrointestinal hormones, adipokines, angiopoietin-like proteins, and microRNAs. These factors play an important role in obesity by controlling fat metabolism, energy homeostasis, food intake, and insulin sensitivity. AMPK is a heterotrimeric serine/threonine protein kinase known as a fuel-sensing enzyme. The central role of AMPK in obesity makes it an attractive molecule to target obesity and related metabolic diseases. In this review, the critical role of AMPK in obesity and the interplay between AMPK and obesity-associated factors were elaborated.

Chicoric acid does not restore palmitate-induced decrease in irisin levels in PBMCs of newly diagnosed patients with T2D and healthy subjects.

Targeting irisin as a myokine/adipokine is a new therapeutic approach in the improvement of insulin-resistance (IR) during type 2 diabetes (T2D). In present study we evaluated the effects of palmitate and chicoric acid (CA) on irisin production in peripheral blood mononuclear cells (PBMCs) of patients with T2D. This study performed on 20 newly diagnosed patients with T2D and 20 healthy subjects. PBMCs treated with palmitate and CA. PPARGC1A and FNDC5 genes expression assessed using qRT-PCR. Irisin levels in cell culture medium measured by ELISA. Palmitate decreased PPARGC1A and FNDC5 genes expression, as well as irisin levels in PBMCs from T2D and healthy volunteers. CA significantly restored palmitate-induced decrease in PPARGC1A gene expression in PBMCs of healthy subjects. Although, FNDC5 gene expression and irisin levels were not induced significantly by CA. In conclusion, palmitate decreases irisin production through down-regulation of PPARGC1A and FNDC5 expressions. However, CA does not effect on irisin pathway.Key pointsPalmitate reduced PPARGC1A and FNDC5 genes expression, as well as irisin secretion in PBMCs.Palmitate-induced decrease in PPARGC1A gene expression significantly has been reversed by CA in PBMCs of healthy subjects.CA did not return palmitate-decreased in FNDC5 gene expression and irisin levels in PBMCs.

Angiopoietin-Like Proteins 2 and 3 in Children and Adolescents with Obesity and Their Relationship with Hypertension and Metabolic Syndrome.

BACKGROUND: Angiopoietin-like protein 2 (ANGPTL2) is one of the adipocyte-derived inflammatory factors which connects obesity to insulin resistance. ANGPTL3 has a direct role in regulation of lipid metabolism. The objective of this study was to evaluate ANGPTL2 and ANGPTL3 in childhood obesity and their relationship with metabolic syndrome. METHODS: 70 children and adolescents, 35 obese and 35 normal-weight subjects, were enrolled in this research after complete clinical examination and anthropometric evaluations. Serum ANGPTL2 and ANGPTL3 and insulin were measured by enzyme-linked immunosorbent assay (ELISA). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate insulin resistance (IR). Colorimetric methods were used for the assessment of fasting plasma glucose (FPG), LDL-C, HDL-C, total cholesterol (TC), and triglyceride (TG). RESULTS: The levels of ANGPTL2 and ANGPTL3 were significantly higher in obese subjects than those in controls, but they did not differ significantly in subjects with or without IR. ANGPTL3 was found to be significantly elevated in obese children with metabolic syndrome (MetS) in comparison with those without MetS. Both of the studied ANGPTLs were positively correlated with BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, and LDL-C. The correlation between ANGPTL3 and either TC or LDL-C remained significant after adjusting for BMI. CONCLUSION: Serum ANGPTL2 and ANGPTL3 were elevated in obesity and associated with blood pressure and indices of metabolic syndrome, suggesting that they might be involved in the advancement of obesity-related hypertension and metabolic syndrome.

Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl4-induced liver fibrosis in rats.

Objectives: In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX).Materials and methods: The six-week old Wistar rats received carbon tetrachloride (CCl4) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured.Results: Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together.Conclusion: The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.

Investigation of oxidative stress markers and antioxidant enzymes activity in newly diagnosed type 2 diabetes patients and healthy subjects, association with IL-6 level.

OBJECTIVE: Oxidative stress and inflammation play an important role in the pathogenesis of diabetes and its complication. In this study, we aimed to evaluate and compare oxidative stress markers and antioxidant enzymes activity, as well as Interleukin 6 (IL-6) level in newly diagnosed type 2 diabetes mellitus (T2DM) patients and healthy subjects. MATERIAL AND METHODS: 30 newly diagnosed type 2 diabetes patients and 30 healthy subjects (age and sex matched) were recruited in this study. After anthropometric parameters measurement, blood sample were collected from all participant. Serum and plasma were isolated. Biochemical parameters were evaluated in serum. Plasma was used to measure malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. Also, IL-6 level was investigated in plasma using ELISA method. RESULTS: MDA and TOS levels were significantly higher in T2DM patients than the control group (p < 0.05). However, TAC and SOD were significantly lower in T2DM as compared with healthy subjects (p < 0.05). Also, IL-6 level was higher in T2DM in comparison to healthy subjects (p = 0.004). Furthermore, there was a significant positive correlation between IL-6 with MDA (p = 0.031, r = 0.482) and TOS (p < 0.001, r = 0.744). In addition, a negative correlation was observed between IL-6 and SOD activity (p = 0.002, r = -0.660). CONCLUSION: Reducing oxidative stress and inflammation could be effective in improvement of T2DM.

Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance.

Background Obesity is associated with oxidative stress. Superoxide dismutase (SOD) is the first line of defense against reactive oxygen species (ROS), eliminating the strong superoxide radical and producing H2O2, which can then be degraded by catalase (CAT). The main objective of this study was to evaluate the gene expression antioxidant enzymes (Mn-SOD and CAT) in peripheral blood mononuclear cells (PBMCs) of obese and normal-weight children, and its association with anthropometric and biochemical parameters. Methods Thirty obese and 30 control subjects between the ages of 8 and 16 years were enrolled in this study. Serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Biochemical parameters were also measured. PBMCs of the subjects were separated and Mn-SOD and CAT gene expression was measured using real-time polymerase chain reaction (PCR). Results Mn-SOD and CAT gene expression was significantly lower in the obese group compared with the control group (p<0.01). Also, a positive correlation was observed between the gene expression of Mn-SOD and CAT and body mass index (BMI), fasting blood sugar, insulin resistance, low density lipoprotein-cholesterol (LDL-C) cholesterol, triglycerides (TG) and systolic blood pressure (SBP). Conclusions Induction of antioxidants, especially Mn-SOD and CAT, can lead to reduction of oxidative stress and prevent the complications of obesity in children.

Reduced gene expression of sirtuins and active AMPK levels in children and adolescents with obesity and insulin resistance.

BACKGROUND: Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents. MATERIALS AND METHODS: Participants included 60 children and adolescents (30 obese and 30 age- and gender-matched control subjects). Real-time polymerase chain reaction (PCR) was used to assess the SIRT1 and SIRT2 gene expression in PBMCs. Serum phospho-AMPK and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the Homeostasis Model of Assessment of Insulin Resistance (HOMA-IR). Glucose and lipid profile were also measured. RESULTS: SIRT1 gene expression and phospho-AMPK plasma levels were significantly diminished in obese subjects compared to the control group, and both SIRT1 and SIRT2 were significantly lower in obese children with IR compared to those without IR. SIRT1 expression revealed significant negative correlations with body mass index and waist circumference as well as insulin and HOMA-IR and a positive correlation with AMPK. SIRT2 negatively correlated with SIRT1 and positively correlated with high density lipoprotein-cholesterol (HDL-C). CONCLUSION: SIRT1 and SIRT2 expression and AMPK levels decrease in children with obesity and IR. Targeting SIRT1 can be valuable in preventing obesity-associated IR in childhood and adolescence.