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Vitamin D levels as an important predictor for type 2 diabetes mellitus and weight regain post-sleeve gastrectomy
Weight Loss Surgery (WLS), including sleeve-gastrectomy (SG), results in significant weight loss and improved metabolic health in severe obesity (BMI ≥ 35 kg/m2). Previous studies suggest post-operative health benefits are impacted by nutrient deficiencies, such as Vitamin D (25(OH)D) deficiency, while it is currently unknown whether nutrient levels may actually predict post-surgery outcomes. As such, this study investigated whether 25(OH)D levels could predict metabolic improvements in patients who underwent SG. Patients with severe obesity (n = 309; 75% female) undergoing SG participated in this ethics-approved, non-randomized retrospective cohort study. Anthropometry, clinical data, 25(OH)D levels and serum markers were collected at baseline, 6-, 12- and 18-months post-surgery. SG surgery resulted in significant improvements in metabolic health at 6- and 12-months post-surgery compared with baseline, as expected. Patients with higher baseline 25(OH)D had significantly lower HbA1c levels post-surgery (p < 0.01) and better post-surgical T2DM outcomes, including reduced weight regain (p < 0.05). Further analysis revealed that baseline 25(OH)D could predict HbA1c levels, weight regain and T2DM remission one-year post-surgery, accounting for 7.5% of HbA1c divergence (p < 0.01). These data highlight that higher circulating 25(OH)D levels are associated with significant metabolic health improvements post-surgery, notably, that such baseline levels are able to predict those who attain T2DM remission. This highlights the importance of 25(OH)D as a predictive biomarker of post-surgery benefits
Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells
In obesity, excess nutrients can disrupt protein folding in the endoplasmic reticulum (ER) which activates the unfolded protein response (UPR) and alters mitochondrial function. These changes can induce inflammation, oxidative stress and insulin resistance. The aim of the study was to investigate whether broccoli extract can protect against cellular damage in human adipocytes, which with mathematical modelling may help predict pathway response. Differentiated Chub-S7 cells were treated over a 72 hr time course with 10 ng/ml freeze-dried broccoli extract (hybrid Brassica oleracea var. italic) alone or combined with ER stress inducer, tunicamycin (750 ng/ml). UPR markers (ATF6, ATF4, CHOP, ERO1α, P-PERK, PERK, P-eIF2α, eIF2α, P-IRE1α and IRE1α) were measured by qRT-PCR and Western blot. Mitochondrial genes (MFN2, OPA1, UCP2, SOD2, POLG) were also measured. Mathematical modelling was undertaken. Tunicamycin led to a significant increase in UPR gene expression (P<0.05), whilst broccoli extract combined with tunicamycin significantly reduced the expression of UPR markers compared with those treated only with tunicamycin, in a time dependent manner. Tunicamycin had a detrimental effect on mitochondrial genes (P<0.05); the presence of broccoli appeared to protect against these effects. This in-vitro time-series data are being used to realistically parameterise an existing mathematical model. Broccoli extract appears to positively influence protein folding in ER stressed adipocytes, reducing UPR gene expression and causing influential changes in mitochondria. As such broccoli supplementation in the daily diet may reduce the inflammatory response posed by adipose tissue during weight gain. The mathematical model of the UPR offers the possibility of in silico optimisation for the supplementation.N/