NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity
| Autor: | Astrid L. Basse, Julia Peics, Iuliia Karavaeva, Karen Nørgaard Nielsen, Tao Ma, Jonas T. Treebak, Sabina Chubanava, Zachary Gerhart-Hines, Oksana Dmytriyeva, Morten Dall |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
eWAT epididymal white adipose tissue Male Nicotinamide phosphoribosyltransferase Adipose tissue Nicotinamide adenine dinucleotide Adipose plasticity Glucose homeostasis NAMPT Energy homeostasis Fgf21 Fibroblast growth factor 21 GTT Glucose tolerance test chemistry.chemical_compound Mice Fibrosis Loss of Function Mutation FANKO Fat-specific Nampt knockouts Nicotinamide Phosphoribosyltransferase Cells Cultured 2. Zero hunger Adipose metabolism TG triglyceride AUC Area under curve NAD+ Nicotinamide adenine dinucleotide Adipose Tissue RER Respiratory exchange rate Cytokines Bmp8b Bone morphogenetic factor 8b lcsh:Internal medicine medicine.medical_specialty Dietary lipid Biology Brief Communication Diet High-Fat 03 medical and health sciences HFD High fat diet Internal medicine scWAT subcutaneous white adipose tissue medicine Animals Obesity lcsh:RC31-1245 Molecular Biology iBAT interscapular brown adipose tissue Cell Biology MR Magnetic resonance medicine.disease NAD NAD+ synthesis Mice Inbred C57BL 030104 developmental biology Endocrinology Glucose chemistry NAD+ kinase Energy Metabolism Nampt Nicotinamide phosphoribosyltransferase |
| Zdroj: | Molecular Metabolism Nielsen, K N, Peics, J, Ma, T, Karavaeva, I, Dall, M, Chubanava, S, Basse, A L, Dmytriyeva, O, Treebak, J T & Gerhart-Hines, Z 2018, ' NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity ', Molecular Metabolism, vol. 11, pp. 178-188 . https://doi.org/10.1016/j.molmet.2018.02.014 Molecular Metabolism, Vol 11, Iss, Pp 178-188 (2018) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2018.02.014 |
| Popis: | Objective The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+) biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) supports adipose plasticity and the pathological progression to obesity. Methods We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results Fat-specific Nampt knockout (FANKO) mice were completely resistant to high fat diet (HFD)-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions These findings indicate that adipose NAMPT plays an essential role in handling dietary lipid to modulate fat tissue plasticity, food intake, and systemic glucose homeostasis. Graphical abstract Highlights • Fat-specific Nampt knockout (FANKO) does not alter body composition on chow diet. • NAMPT is essential for adipose expansion and weight gain from high dietary fat. • Loss of adipose NAD+ decreases food intake and improves glucose tolerance. • High fat diet-induced metabolic dysfunction in FANKO mice is reversible. |
| Databáze: | OpenAIRE |
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