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Publication : Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain.

First Author  Page MM Year  2018
Journal  FASEB J Volume  32
Issue  3 Pages  1196-1206
PubMed ID  29122848 Mgi Jnum  J:270193
Mgi Id  MGI:6277348 Doi  10.1096/fj.201700518R
Citation  Page MM, et al. (2018) Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain. FASEB J 32(3):1196-1206
abstractText  Excess circulating insulin is associated with obesity in humans and in animal models. However, the physiologic causality of hyperinsulinemia in adult obesity has rightfully been questioned because of the absence of clear evidence that weight loss can be induced by acutely reversing diet-induced hyperinsulinemia. Herein, we describe the consequences of inducible, partial insulin gene deletion in a mouse model in which animals have already been made obese by consuming a high-fat diet. A modest reduction in insulin production/secretion was sufficient to cause significant weight loss within 5 wk, with a specific effect on visceral adipose tissue. This result was associated with a reduction in the protein abundance of the lipodystrophy gene polymerase I and transcript release factor ( Ptrf; Cavin) in gonadal adipose tissue. RNAseq analysis showed that reduced insulin and weight loss also associated with a signature of reduced innate immunity. This study demonstrates that changes in circulating insulin that are too fine to adversely affect glucose homeostasis nonetheless exert control over adiposity.-Page, M. M., Skovso, S., Cen, H., Chiu, A. P., Dionne, D. A., Hutchinson, D. F., Lim, G. E., Szabat, M., Flibotte, S., Sinha, S., Nislow, C., Rodrigues, B., Johnson, J. D. Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain.
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