The effect of chronic oral vitamin D supplementation on adiposity and insulin secretion in hypothalamic obese rats

Abstract

Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.

Dietary Magnesium Intake Level Modifies the Association Between Vitamin D and Insulin Resistance: A Large Cross-Sectional Analysis of American Adults

“…Low magnesium (2+) levels lead to defective tyrosine kinase activity, and insulin acts on receptors that are later damaged, altering cellular glucose transport and reducing cellular glucose utilization, thereby promoting peripheral IR in type 2 diabetes ( 21 , 40 ). In addition, our finding is also consistent with another cross-sectional analysis conducted in the NHANES that magnesium intakes interact with serum Vit D levels in relation to type 2 diabetes ( 36 ). Thus, magnesium supplementation has the potential to increase Vit D activity such that it increases Vit D’s protection of pancreatic β-cells.…”

“…It has been reported that reduced plasma Vit D levels may produce excessive white adipose tissue, leading to IR and dyslipidemia ( 36 ). In a cross-sectional analysis conducted by Bilge et al ( 37 ) in 2015 on a Turkish population of 39 individuals with normal weights and 66 individuals categorized as obese, Vit D was found to be negatively associated with the modified HOMA-IR index after adjusting for laboratory indicators, physical measurements, and other factors Research conducted by Wang et al ( 38 ) also found that Vit D deficiency may lead to increased activity of the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway, which promotes inflammation and leads to IR.…”

Vitamin D and Obesity/Adiposity—A Brief Overview of Recent Studies

“…Conversely, some studies have reported no effect of VD supplementation or VD deficiency on body weight, adiposity, or adipose tissue fat pad mass [ 56 , 57 , 59 , 61 , 77 , 78 , 79 ], whereas other studies reported that VD deficiency decreased HF diet-induced obesity in rodents [ 80 , 81 , 82 ]. The lack of clear-cut results is problematic, and the origin of these discrepancies remains partly unexplained.…”

Conundrum of vitamin D on glucose and fuel homeostasis

“…Several molecular mechanisms were proposed to account for the effects of vitamin D on beta cells, including changes in the local pancreatic islet renin-angiotensin system[ 155 ], restoration of GLUT2 expression[ 156 ], enhancement of IP3 and AMPA receptor expression[ 157 ], vitamin D-binding protein-induced beta cell dedifferentiation[ 158 ], reduction of oxidative damage[ 159 ], reduced cholinergic pancreatic effects[ 160 ], enhanced transcriptional regulation of voltage-gated calcium channels[ 161 ], and elevation of PPAR-γ expression[ 162 ]. However, further studies are required to confirm the proposed mechanisms.…”