Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D-3 [25(OH)D-3] as well as plasma 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity. Objective: To investigate the association between body mass index (BMI) and plasma 25(OH)D-3 and 1,25(OH)(2)D-3, AT VDR; between plasma 25(OH)D-3, 1,25(OH)(2)D-3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity. Design and Patients: This analysis included 92 adult individuals (BMI, >25 kg/m(2)). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H(2)]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR. Setting: University medical center. Main Outcome Measures: Plasma 25(OH)D-3, 1,25(OH)(2)D-3, 1,25(OH)(2)D-3/25(OH)D-3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity. Results: BMI was inversely associated with plasma 25(OH)D-3 (beta = 20.274; P = 0.011) but not with plasma 1,25(OH)(2)D-3. Plasma 25(OH)D-3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)(2)D-3 and 25(OH)D-3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (b = 20.207; P = 0.025). Conclusions: BMI was inversely associated with 25(OH)D-3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity

Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model

Background and aims: Gut derived short-chain fatty acids (SOFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SOFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SOFA, we aimed to investigate the in vitro effects of SOFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells. Methods: hMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SOFA (acetate, propionate and butyrate) in concentrations ranging between 1 mu mol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following p-adrenergic stimulation. Results: SOFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, p-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SOFA mixtures. Incubation with only acetate decreased basal (1 mu mol/L) and p-adrenergically (1 mmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 mu mol/L) slightly increased basal and p-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SOFA and acts via attenuation of HSL phosphorylation in a Gi coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism

Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model

Background and aims: Gut derived short-chain fatty acids (SOFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SOFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SOFA, we aimed to investigate the in vitro effects of SOFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells. Methods: hMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SOFA (acetate, propionate and butyrate) in concentrations ranging between 1 mu mol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following p-adrenergic stimulation. Results: SOFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, p-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SOFA mixtures. Incubation with only acetate decreased basal (1 mu mol/L) and p-adrenergically (1 mmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 mu mol/L) slightly increased basal and p-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SOFA and acts via attenuation of HSL phosphorylation in a Gi coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism

Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model

Background and aimsGut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells.MethodshMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 µmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following β-adrenergic stimulation.ResultsSCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P &lt; 0.05), while mixtures high in butyrate had no effect. Also, β-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 µmol/L) and β-adrenergically (1 µmol/L and 1 mmol/L) mediated glycerol release when compared with control (P &lt; 0.05). In contrast, butyrate (1 µmol/L) slightly increased basal and β-adrenergically mediated glycerol release compared with control (P &lt; 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate.ConclusionThe present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi-coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism

Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity

Context: Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D-3 [25(OH)D-3] as well as plasma 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity. Objective: To investigate the association between body mass index (BMI) and plasma 25(OH)D-3 and 1,25(OH)(2)D-3, AT VDR; between plasma 25(OH)D-3, 1,25(OH)(2)D-3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity. Design and Patients: This analysis included 92 adult individuals (BMI, >25 kg/m(2)). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H(2)]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR. Setting: University medical center. Main Outcome Measures: Plasma 25(OH)D-3, 1,25(OH)(2)D-3, 1,25(OH)(2)D-3/25(OH)D-3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity. Results: BMI was inversely associated with plasma 25(OH)D-3 (beta = 20.274; P = 0.011) but not with plasma 1,25(OH)(2)D-3. Plasma 25(OH)D-3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)(2)D-3 and 25(OH)D-3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (b = 20.207; P = 0.025). Conclusions: BMI was inversely associated with 25(OH)D-3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity