Salmon peptides limit obesity-associated metabolic disorders by modulating a gut-liver axis in vitamin D-deficient mice.

OBJECTIVE: This study investigated the effects of a low-dose salmon peptide fraction (SPF) and vitamin D3 (VitD3 ) in obese and VitD3 -deficient mice at risk of metabolic syndrome (MetS). METHODS: Obese and VitD3 -deficient low-density lipoprotein receptor (LDLr)-/- /apolipoprotein B100 (ApoB)100/100 mice were treated with high-fat high-sucrose diets, with 25% of dietary proteins replaced by SPF or a nonfish protein mix (MP). The SPF and MP groups received a VitD3 -deficient diet or a supplementation of 15,000 IU of VitD3 per kilogram of diet. Glucose homeostasis, atherosclerosis, nonalcoholic fatty liver disease, and gut health were assessed. RESULTS: VitD3 supplementation increased plasma 25-hydroxyvitamin D to optimal status whereas the VitD3 -deficient diet maintained moderate deficiency. SPF-treated groups spent more energy and accumulated less visceral fat in association with an improved adipokine profile. SPF lowered homeostatic model assessment of insulin resistance compared with MP, suggesting that SPF can improve insulin sensitivity. SPF alone blunted hepatic and colonic inflammation, whereas VitD3 supplementation attenuated ileal inflammation. These effects were associated with changes in gut microbiota such as increased Mogibacterium and Muribaculaceae. CONCLUSIONS: SPF treatment improves MetS by modulating hepatic and gut inflammation along with gut microbiota, suggesting that SPF operates through a gut-liver axis. VitD3 supplementation has limited influence on MetS in this model.

Vitamin D reduces LPS-induced cytokine release in omental adipose tissue of women but not men.

CONTEXT: Both vitamin D deficiency and inflammation have been associated with insulin resistance and type 2 diabetes risk. In vitro vitamin D treatment of subcutaneous (SC) adipose tissue (AT) may reduce inflammation, but data are conflicting. OBJECTIVES: To evaluate the effects of vitamin D (25(OH)D3 and 1,25(OH)2D3) on the secretion of inflammatory cytokines (TNF-α and IL-6) in omental (OM) and SC human AT and to explore factors that could correlate with the individual response to vitamin D including age, smoking status, BMI, comorbidities, medication, HbA1c, apolipoprotein B, serum 25-hydroxyvitamin D and high sensitivity C-reactive protein. PATIENTS: 7 men and 8 women with severe obesity undergoing bariatric surgery. INTERVENTION: Fresh OM and SC AT explants sampled during surgery (n=15) were incubated for 24h in a control, 25(OH)D3 (150 nM) or 1,25(OH)2D3 (1 nM) medium. Lipopolysaccharide (LPS) (10 ng/ml) was added for another 24h. MAIN OUTCOME MEASURE: Change in TNF-α and IL-6 levels in collected media after vitamin D treatment (ELISA). RESULTS: Mean age and BMI of the patients were 46.4±10.9 years and 48.8±7.5 kg/m(2), respectively. Eleven patients had type 2 diabetes. 25(OH)D3 and 1,25(OH)2D3 reduced the LPS-induced increases in cytokine levels in OM AT of women but not in men. No effect was observed in SC AT. Apart from gender, none of the factors analyzed correlated with vitamin D response. CONCLUSION: We showed that 25(OH)D3 and 1,25(OH)2D3 can lower cytokine release from OM but not SC AT explants and only in women.