Vitamin D₃supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR^−/−and LDLR^+/+mice

Abstract

IntroductionFatty liver disease is prevalent in populations with high caloric intake. Nutritherapeutic approaches are being considered, such as supplementary Vitamin D3, to improve aspects of metabolic syndrome, namely fatty liver disease, hyperlipidemia, and insulin resistance associated with obesity.MethodsWe analyzed female LDLR−/− and LDLR+/+ mice on a 10‐week diabetogenic diet for markers of fatty liver disease, metabolic strain, and inflammation.ResultsThe groups on a high fat high sugar diet with supplementary Vitamin D3, in comparison with the groups on a high fat high sugar diet alone, showed improved transaminase levels, significantly less hypertriglyceridemia and hyperinsulinemia, and histologically, there was less pericentral hepatic steatosis. Levels of non‐esterified fatty acids and lipid peroxidation products were significantly lower in the group supplemented with additional Vitamin D3, as were systemic markers of inflammation (serum endotoxin and IL‐6). M2 macrophage phenotype predominated in the group supplemented with additional Vitamin D3. Beneficial changes were observed as early as five weeks’ supplementation with Vitamin D3 and extended to restoration of high fat high sugar diet induced decrease of bone mineral density.ConclusionIn summary, Vitamin D3 was a significantly beneficial dietary additive to blunt a prediabetic phenotype in diet‐induced obesity of female LDLR−/− and LDLR+/+ mice.

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

“…Similar results were recently reported by Jin et al (49) using intraperitoneal VD administration in MSG-obese rats. VD supplementation also improved the metabolic profile in HFD-obese mice and in LDL receptor knockout mice (8) . The association between VD and lipid profiles, including TAG, was demonstrated in a longitudinal study by Jorde et al (55) .…”

“…Thus, obesity and the metabolic syndrome are conditions intimately related to the development of type 2 diabetes mellitus and CVD worldwide (7,(9)(10)(11) . It has been demonstrated that VD supplementation could improve glucose tolerance, pancreatic β-cell function and insulin sensitivity (6)(7)(8)12,13) , although these actions have not been confirmed by all authors (14)(15)(16)(17) . VD has direct effects on the endocrine pancreas (12) .…”

“…Several common conditions, such as low sunshine exposure, malabsorption and ageing, are related to VD deficiency (6) . However, in recent decades the associations between excessive white adipose tissue (WAT) content and VD deficiency have been observed in some studies (1,3) , a condition that could favour the metabolic abnormalities present in obesity (7,8) . In this regard, obesity is an important component of the metabolic syndrome, defined as the association of insulin resistance (IR), glucose intolerance (9) , dyslipidaemia, hypertension and excessive WAT visceral content (10) .…”

“…In the pancreatic β-cell, the presence of VDR and the expression of 1α-hydroxylase enzyme is well established (5,14,18,19) . Rodents with VD depletion present impaired insulin secretion (8,13) . Moreover, glucose-induced insulin secretion (GIIS) is diminished in islets from VDR-mutant mice (5,18) .…”

Neuroprotective effects of vitamin D on high fat diet- and palmitic acid-induced enteric neuronal loss in mice

“…VD mediates anti-inflammatory effects and has been shown to reduce HFD-induced increases in tumor necrosis factor α (TNFα) and pro-inflammatory cytokines such as interleukin (IL) -6 and lipid peroxidation products [ 60 , 61 ]. Besides anti-inflammatory effects VD has also been shown to have anti-oxidative effects by expression of anti-oxidative enzymes such as superoxide dismutase (SOD), glutathione (GSH), and catalase [ 21 , 22 ].…”