Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal
| Autor: | Tanya Tarnovscki, Hagit Shapiro, Noa Slutsky, Avishai Shemesh, Maayan Vatarescu, Assaf Rudich, Tal Pecht, Nava Bashan, Angel Porgador, Ori Nov, Yulia Haim, Sapir Bechor |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Adipose tissue macrophages Adipose tissue Blood sugar 030209 endocrinology & metabolism Inflammation 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Insulin resistance Internal medicine insulin resistance Weight Loss medicine Glucose homeostasis Animals Obesity adipose tissue inflammation Chemistry obesity reversal Insulin Research Macrophages Lipid metabolism medicine.disease Lipid Metabolism Mice Inbred C57BL 030104 developmental biology Adipose Tissue Gene Expression Regulation Liver medicine.symptom adipose tissue macrophages glucose production |
| Zdroj: | The Journal of Endocrinology |
| ISSN: | 1479-6805 0022-0795 |
| Popis: | Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages. |
| Databáze: | OpenAIRE |
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