Modulation of the human preadipocyte mitochondrial activity by beta-carotene

Increased ROS generation by the overload by metabolic substrates mitochondria paralleled by decrease of antioxidant activity are typical events found in metabolic syndrome and diabetes type 2. Metabolites of beta-carotene (BC) such as retinoic acid (RA), as well as low concentration of reactive oxygen species (ROS) modify the mitochondrial bioenergetic function. The aim of the study was to investigate the effect of beta-carotene on mitochondrial activity in human preadipocytes. BC used in concentrations, 10 or 30 µM, decreased mitochondrial membrane potential, inhibited mitochondrial respiration and decreased cellular ATP content. We conclude, that BC, the known antioxidant may decrease oxidative phosphorylation capacity of mitochondria

Glucagon-like peptide-1 receptor agonist stimulates mitochondrial bioenergetics in human adipocytes

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions. For this purpose, preadipocytes CHUBS7 were differentiated to mature adipocytes and then stimulated with GLP-1RA, exendin-4 at 100 nM for 24 h. Oxygen consumption rates, mitochondrial membrane potential, intracellular ATP (adenosine triphosphate) level, SIRT1 and SIRT3 gene expression and the histone deacetylases' activity were measured. Exendin-4 was found to uncouple mitochondrial electron transport from ATP synthesis, slightly decreasing mitochondrial membrane potential in mature adipocytes. Routine respiration and uncoupled oxy- gen consumption rates were higher in exendin-4 treated adipocytes than in the non-treated cells. The ATP level remained unchanged. Exendin-4 enhanced SIRT1 and SIRT3 genes expression. Histone deacetylases' activity in the nuclear fraction was not affected by exendin-4, although the activity of class III histone deacetylases was increased. All of the effects on mitochondrial bioenergetics induced by exendin-4 were abolished by addition of glucagon-like peptide 1 receptor antagonist. In conclusion, exendin-4 activates the sirtuin pathway and increases energy expenditure in human adipocytes. Our results suggest another mechanism that may be responsible for body weight reduction observed in patients using GLP-1RAs

High fat mixed meal tolerance test leads to suppression of osteocalcin decrease in obese insulin resistant subjects compared to healthy adults

Nutrients influence bone turnover. Carboxylated osteocalcin (Gla-OC) participates in bone formation whereas its undercarboxylated form (Glu-OC) acts as a hormone in glucose metabolism. The aim of the study was to determine the responses of Gla-OC, Glu-OC, and total-OC (calculated as the sum of Gla-OC and Glu-OC) to a high fat mixed meal tolerance test (HFMTT) in non-obese (body mass index (BMI) < 30 kg/m2, n = 24) and obese subjects (30 < BMI < 40 kg/m2, n = 70) (both sexes, aged 25⁻65 years). Serum Gla-OC and Glu-OC were measured at baseline as well as at 2 and 6 h during a HFMTT by enzyme-linked immunosorbent assay (ELISA). Baseline Gla-OC, Glu-OC, and total-OC levels were lower in obese individuals compared to non-obese participants (p = 0.037, p = 0.016 and p = 0.005, respectively). The decrease in Gla-OC and total-OC, but not in Glu-OC, concentrations during the HFMTT was suppressed in obese, but not in non-obese controls (p < 0.05, p < 0.01, p = 0.08, respectively). Subjects with the highest homeostatic model assessment for insulin resistance (HOMA-IR) index values had a less pronounced decrease in total-OC compared to patients with values of HOMA-IR index in the 1st quartile (p < 0.05). Net incremental area under Gla-OC inversely correlated with adiponectin (rho = −0.35, p = 0.001). Increase in insulin sensitivity and adiponectin level in obese subjects could beneficially influence postprandial bone turnover expressed by osteocalcin concentration

Carboxylated and undercarboxylated osteocalcin in metabolic complications of human obesity and prediabetes

Background Carboxylated osteocalcin (Gla‐OC) participates in bone remodeling, whereas the undercarboxylated form (Glu‐OC) takes part in energy metabolism. This study was undertaken to compare the blood levels of Glu‐OC and Gla‐OC in nonobese, healthy obese, and prediabetic volunteers and correlate it with the metabolic markers of insulin resistance and early markers of inflammation. Methods Nonobese (body mass index [BMI] <30 kg/m2 ; n = 34) and obese subjects (30 <BMI <40 kg/m2 ; n = 98), both sexes, aged 25 to 65 years, were divided into healthy control, normal weight subjects, healthy obese, and obese with biochemical markers of prediabetes. The subgroups with obesity and low or high Gla‐OC or Glu‐OC were also considered for statistical analysis. After 2 weeks of diet standardization, venous blood was sampled for the determination of Gla‐OC, Glu‐OC, lipid profile, parameters of inflammation (hsCRP, interleukin 6, sE‐selectin, sPECAM‐1, and monocyte chemoattractant protein 1), and adipokines (leptin, adiponectin, visfatin, and resistin). Results Gla‐OC in obese patients was significantly lower compared to nonobese ones (11.36 ± 0.39 vs 12.69 ± 0.90 ng/mL, P = .048) and weakly correlated with hsCRP (r = −0.18, P = .042), visfatin concentration (r = −0.19, P = .033), and BMI (r = −0.17, P = .047). Glu‐OC was negatively associated with fasting insulin levels (r = −0.18, P = .049) and reduced in prediabetic individuals compared with healthy obese volunteers (3.04 ± 0.28 vs 4.48 ± 0.57, P = .025). Conclusions Decreased blood concentration of Glu‐OC may be a selective early symptom of insulin resistance in obesity, whereas the decreased level of Gla‐OC seems to be associated with the appearance of early markers of low grade inflammation accompanying obesity