Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D

Biochemical and Biophysical Research Communications
K Hoa NguyenSuresh Mishra

Abstract

The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both...Continue Reading

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Citations

Jun 28, 2016·Biology of Sex Differences·K Hoa NguyenSuresh Mishra
Apr 13, 2017·Experimental Biology and Medicine·Suresh Mishra, Bl Grégoire Nyomba
Dec 22, 2017·Signal Transduction and Targeted Therapy·Sudharsana Rao AndeSuresh Mishra
Jul 31, 2018·Endocrine Reviews·Karen D CorbinUNKNOWN Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)
Feb 6, 2019·Experimental Biology and Medicine·Suresh Mishra, Bl Grégoire Nyomba

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