Acute Vitamin D3 Supplementation in Severe Obesity: Evaluation of Multimeric Adiponectin

Abstract

Obesity predisposes to vitamin D deficiency (VDD) and glucose abnormalities. It is currently debated if vitamin D administration may improve glucose homeostasis by interacting with modulators of insulin sensitivity, such as adiponectin and its oligomers. In a 4-week inpatient study on a metabolic rehabilitation program, consisting of individualized caloric restriction and aerobic physical exercise in obese subjects with VDD, we assessed the acute effects of 600,000 IU cholecalciferol given per os VD group, 12 subjects; body mass index (BMI) 42.7 ± 1.3 kg/m2) or placebo per os (PL group, 12 subjects, BMI 39.8 ± 0.9 kg/m2) on high (HWM-A), medium (MMW-A), and low molecular weight adiponectin (LMW-A), as quantified by western immunoblot (WIB) and ELISA. During the 4-week study, dieting promoted a similar magnitude of weight loss in VD and PL groups. Compared to the PL group, cholecalciferol administration increased 25(OH)Vit D levels (p < 0.001) and promoted a significant increase of HMW-A expression analyzed by WIB (p = 0.02). In parallel, a significant decrease of leptin/HMW-A ratio (p < 0.05), a biomarker of metabolic homeostasis, was observed. During the study, changes of MMW-A and LMW-A occurred independently of cholecalciferol administration, and were likely explained by weight loss. At odds with these findings, the ELISA assessment of adiponectin oligomers showed no modifications in the VD group or PL group. Current findings suggest that acute cholecalciferol administration selectively modifies HMW-A and the leptin/HMW-A ratio.

The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity

“…This interaction suggests the intervention of body composition-independent neuroendocrine signals controlling energy metabolism via THs. Because our study did not include the measurement of circulating leptin, which is rapidly responsive to weight loss [ 57 ] and regulates the thermogenic activity through central mechanisms involving TRH [ 3 , 58 , 59 ] our results provide no insight on neuroendocrine control of TH-REE association during weight loss.…”

Fetuin B links vitamin D deficiency and pediatric obesity: Direct negative regulation by vitamin D

“…More importantly, FETUB localizes to the identical cytogenetic band where adiponectin is found, 3q27.3 [ 46 ]. Adiponectin has recently been demonstrated to be significantly reduced in VDD pediatric obese subjects and to be directly upregulated by VD administration [ 15 , 28 ]. To understand if SSP4202 could be FETUB, 2DE western immunoblots of plasma using IPG4–7 strips and a FETUB-specific antibody were performed, in which 5 isoforms of FETUB were clearly observed ( Fig.…”

“…With the demonstration that VDD rates closely resemble those of overweight and obesity [ 10 ], evidence is accumulating to suggest that there are clear links between obesity and suboptimal VD levels [ 9 , 11 , 12 ]. For example, an inverse relationship has been repeatedly demonstrated between high body fat and low serum 25-OHD in both adults and children, regardless of the index for body fat used, including BMI [ 11 , [13] , [14] , [15] ], waist circumference [ 16 , 17 ], subcutaneous adipose tissue (sAT [ 16 , 18 ]) and visceral adipose tissue [ 16 , 18 ]. Abnormalities have been observed in adipose tissue (AT)-specific metabolism of VD in adult obese subjects, with the SAT VD metabolic enzymes significantly reduced in adult obese individuals and circulating VD levels increasing by 27% with weight loss [ 19 ].…”

“…Evidence from a bi-directional Mendelian randomized analysis of 21 adult cohorts (42,024 subjects), suggests that a higher BMI is causal for reduced circulating 25OHD levels [ 11 ]. With respects to children, cross-sectional studies have primarily focused on classical cardiometabolic risk factors such as blood pressure, fasting glucose and lipids [ 20 , 21 ], with studies demonstrating a strong association of VDD to hypertension, diabetes and prediabetes [ 15 , [22] , [23] , [24] , [25] ]. None of these studies have been able to decipher the metabolic signals that link a poor VD status to obesity [ 26 , 27 ].…”

New Insights on Low Vitamin D Plasma Concentration as a Potential Cardiovascular Risk Factor.

“…Consistently, the weekly administration of 20,000 IU of cholecalciferol was shown to be ineffective in preventing the progression from prediabetes to T2DM in an RCT conducted on 511 patients. In obese subjects, high-dose cholecalciferol administration was recently shown able to selectively increase plasma levels of high-molecular weight adiponectin, a mediator of glucose homeostasis [172].…”