RESUMO
Sirtuin 5 (SIRT5) plays an important role in the maintenance of lipid metabolism and in white adipose tissue browning. In this study, we established a mouse model for diet-induced obesity and the browning of white fat; combined with gene expression intervention, transcriptome sequencing, and cell molecular biology methods, the regulation and molecular mechanisms of SIRT5 on fat deposition and beige fat formation were studied. The results showed that the loss of SIRT5 in obese mice exacerbated white adipose tissue deposition and metabolic inflexibility. Furthermore, the deletion of SIRT5 in a white-fat-browning mouse increased the succinylation of uncoupling protein 1 (UCP1), resulting in a loss of the beiging capacity of the subcutaneous white adipose tissue and impaired cold tolerance. Mechanistically, the inhibition of SIRT5 results in impaired CCAAT/enhancer binding protein beta (C/EBPß) expression in brown adipocytes, which in turn reduces the UCP1 transcriptional pathway. Thus, the transcription of UCP1 mediated by the SIRT5-C/EBPß axis is critical in regulating energy balance and obesity-related metabolism.
Assuntos
Tecido Adiposo Branco , Proteína beta Intensificadora de Ligação a CCAAT , Obesidade , Transdução de Sinais , Sirtuínas , Proteína Desacopladora 1 , Animais , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Tecido Adiposo Branco/metabolismo , Camundongos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Sirtuínas/metabolismo , Sirtuínas/genética , Obesidade/metabolismo , Obesidade/genética , Tecido Adiposo Marrom/metabolismo , Regulação para Cima , Camundongos Endogâmicos C57BL , Masculino , Metabolismo Energético , Camundongos KnockoutRESUMO
Adipose tissue macrophages (ATM) are an essential type of immune cells in adipose tissue. Obesity induces the inflammation of adipose tissues, as expressed by ATM accumulation, that is more likely to become a source of systemic metabolic diseases, including insulin resistance. The process is characterized by the transcriptional regulation of inflammatory pathways by virtue of signaling molecules such as cytokines and free fatty acids. Notably, posttranslational modification (PTM) is a key link for these signaling molecules to trigger the proinflammatory or anti-inflammatory phenotype of ATMs. This review focuses on summarizing the functions and molecular mechanisms of ATMs regulating inflammation in obese adipose tissue. Furthermore, the role of PTM is elaborated, hoping to identify new horizons of treatment and prevention for obesity-mediated metabolic disease.
Assuntos
Tecido Adiposo , Resistência à Insulina , Animais , Camundongos , Tecido Adiposo/metabolismo , Macrófagos , Obesidade , Resistência à Insulina/fisiologia , Inflamação , Processamento de Proteína Pós-Traducional , Camundongos Endogâmicos C57BLRESUMO
Succinate, one of the intermediates of the tricarboxylic acid cycle, is now recognized to play a role in a broad range of physiological and pathophysiological settings, but its role in adipogenesis is unclear. Our study used Bama miniature pigs as a model to explore the effects of succinate on performance, meat quality, and fat formation. The results showed that adding 1% succinate significantly increased the average daily gain, feed/gain ratio, eye muscle area, and body fat content (p < 0.05), but had no effect on feed intake. Further meat quality analysis showed that succinate increased the marbling score and intramuscular fat content of longissimus dorsi muscle (LM), while decreasing the shear force and the cross-sectional area of LM (p < 0.05). Metabolomics analysis of LM revealed that succinate reshaped levels of fatty acids, triglycerides, glycerophospholipids, and sphingolipids in LM. Succinate promotes adipogenic differentiation in porcine primary preadipocytes. Finally, dietary succinate supplementation increased succinylation modification rather than acetylation modification in the adipose tissue pool. This study elucidated the effects of succinate on the growth and meat quality of pigs and its mechanism of action and provided a reference for the role of succinate in the nutrition and metabolism of pigs.
RESUMO
Excessive fat deposition can cause chicken health problem, and affect production efficiency by causing great economic losses to the industry. However, the molecular underpinnings of the complex adiposity trait remain elusive. In the current study, we constructed and compared the gene co-expression networks on four transcriptome profiling datasets, from two chicken lines under divergent selection for abdominal fat contents, in an attempt to dissect network compositions underlying adipose tissue growth and development. After functional enrichment analysis, nine network modules important to adipogenesis were discovered to be involved in lipid metabolism, PPAR and insulin signaling pathways, and contained hub genes related to adipogenesis, cell cycle, inflammation, and protein synthesis. Moreover, after additional functional annotation and network module comparisons, common sub-modules of similar functionality for chicken fat deposition were identified for different chicken lines, apart from modules specific to each chicken line. We further validated the lysosome pathway, and found TFEB and its downstream target genes showed similar expression patterns along with chicken preadipocyte differentiation. Our findings could provide novel insights into the genetic basis of complex adiposity traits, as well as human obesity and related metabolic diseases.