Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

Autor:	Schmitz J; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Evers N; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Awazawa M; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Nicholls HT; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Brönneke HS; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Dietrich A; Department of Surgery, University of Leipzig, Leipzig, Germany., Mauer J; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany., Blüher M; Department of Medicine, University of Leipzig, Leipzig, Germany., Brüning JC; Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Gleueler Str. 50, D-50931 Cologne, Germany. Electronic address: bruening@sf.mpg.de.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2016 Jan 11; Vol. 5 (5), pp. 328-339. Date of Electronic Publication: 2016 Jan 11 (Print Publication: 2016).
DOI:	10.1016/j.molmet.2015.12.001
Abstrakt:	Objective: Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. Methods: We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Results: Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.
Databáze:	MEDLINE
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