RESUMO
Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acid profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen 3-mo-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 mo. A subgroup of ovariectomized rats received estradiol replacement. RAT samples were analyzed with data-independent acquisitions LC-MS/MS, and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that five pathways were significantly affected by ovariectomy, namely, metabolism of lipids (including fatty acid metabolism and mitochondrial fatty acid ß-oxidation), fatty acyl-CoA biosynthesis, innate immune system (including neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (including ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acid content. The analysis of the data indicated that ovariectomy favored lipogenesis whereas it impaired fatty acid oxidation and induced a proinflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause.
Assuntos
Tecido Adiposo Branco/metabolismo , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/fisiologia , Ovariectomia , Proteômica , Adiposidade/fisiologia , Animais , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Ácidos Graxos/análise , Feminino , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/química , Obesidade , Pós-Menopausa , Ratos , Ratos WistarRESUMO
Carotenoids are lipid-soluble yellow to orange pigments produced by plants, bacteria, and fungi. They are consumed by animals and metabolized to produce molecules essential for gene regulation, vision, and pigmentation. Cave animals represent an interesting opportunity to understand how carotenoid utilization evolves. Caves are devoid of light, eliminating primary production of energy through photosynthesis and, therefore, limiting carotenoid availability. Moreover, the selective pressures that favor carotenoid-based traits, like pigmentation and vision, are relaxed. Astyanax mexicanus is a species of fish with multiple river-adapted (surface) and cave-adapted populations (i.e., Tinaja, Pachón, Molino). Cavefish exhibit regressive features, such as loss of eyes and melanin pigment, and constructive traits, like increased sensory neuromasts and starvation resistance. Here, we show that, unlike surface fish, Tinaja and Pachón cavefish accumulate carotenoids in the visceral adipose tissue. Carotenoid accumulation is not observed in Molino cavefish, indicating that it is not an obligatory consequence of eye loss. We used quantitative trait loci mapping and RNA sequencing to investigate genetic changes associated with carotenoid accumulation. Our findings suggest that multiple stages of carotenoid processing may be altered in cavefish, including absorption and transport of lipids, cleavage of carotenoids into unpigmented molecules, and differential development of intestinal cell types involved in carotenoid assimilation. Our study establishes A. mexicanus as a model to study the genetic basis of natural variation in carotenoid accumulation and how it impacts physiology.
Assuntos
Carotenoides/metabolismo , Characidae/genética , Animais , Evolução Biológica , Carotenoides/análise , Cavernas , Characidae/anatomia & histologia , Characidae/metabolismo , Cromatografia Líquida de Alta Pressão , Mapeamento Cromossômico , Olho/anatomia & histologia , Feminino , Gordura Intra-Abdominal/química , Masculino , Análise de Sequência de DNA , Análise de Sequência de RNA , TranscriptomaRESUMO
BACKGROUND: Obesity is a worldwide prevalent disease and is an underlying factor of non-alcoholic fatty liver disease (NAFLD). It has been understood as a chronic inflammatory state, being associated with the production of adipokines. The aim of this study was to analyze the levels of adipokines in the serum, visceral, and subcutaneous fat and to compare them with hepatic histopathology in morbidly obese patients. METHODS: This is a cross-sectional observational study, which analyzed the findings of liver biopsy in patients undergoing bariatric surgery and who had performed analysis of adipokines mRNA expression (adiponectin-ADIPOQ, leptin-LEP, and resistin-RETN) in subcutaneous and visceral adipose tissue and circulating adipokines in serum. Liver biopsies performed were evaluated according to Kleiner criteria. RESULTS: The study analyzed 25 patients undergoing bariatric surgery. The sample was composed exclusively of women. There was a predominance of NAFLD, with 21 patients (84%) with intrahepatic fat accumulation. Twelve patients presented non-alcoholic steatohepatitis (NASH). Glycated hemoglobin levels (HbA1c) were elevated in NASH patients. ADIPOQ levels were directly correlated with high-density lipoprotein (HDL) cholesterol levels and inversely correlated with triglycerides and total cholesterol. LEP levels showed an inverse relationship with the degree of steatosis, and RETN levels showed an inverse relationship with fibrosis stages. CONCLUSION: Serum LEP levels were reduced in the presence of increased levels of intrahepatic fat, and serum levels of RETN were diminished in the presence of NASH. HbA1c levels were higher in the presence of NASH, indirectly reflecting insulin resistance. Moreover, ADIPOQ levels were related to blood lipid profile.
Assuntos
Adipocinas/sangue , Gordura Intra-Abdominal/química , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/cirurgia , Gordura Subcutânea/química , Adulto , Cirurgia Bariátrica , Biópsia , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Fígado/química , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Gordura Subcutânea/patologiaRESUMO
Background: The results of experimental studies indicate that grafting of autologous adipose tissue may induce tumorigenesis at the recipient site, but clinical results do not support a carcinogenic effect of fat grafting to the breast. Objectives: The authors assessed cancer risk following transplantation of autologous fat into murine mammary tissue. Methods: In this animal study, mammary tissues from 54 breasts of 9 female rats were either grafted with autologous subcutaneous fat, grafted with autologous omental fat, or unmanipulated. Tissues were harvested and processed for histologic and immunohistochemical analyses, and the mRNA expression levels of specific genes were determined. Results: No atypia or changes in lobular structures were observed in lipofilled breasts compared with controls. The numbers of ductal cell layers and terminal ductal units were similar for lipofilled and control breasts. Macrophage concentrations also were similar for the 3 groups. The localization and magnitude of plasminogen activator inhibitor 1 were similar for lipofilled and unmanipulated breast tissue. The percentages of cells expressing Ki67 or estrogen receptor (ER) and the ER/Ki67 balance were similar for the 3 groups. Gene expression was not altered in lipofilled breasts, compared with controls. Conclusions: No theoretical risk of cancer was detected in the microenvironment of the lipofilled rat breast.
Assuntos
Gordura Intra-Abdominal/transplante , Mamoplastia/efeitos adversos , Neoplasias Mamárias Experimentais/etiologia , Gordura Subcutânea/transplante , Transplante de Tecidos/efeitos adversos , Microambiente Tumoral , Animais , Mama/química , Mama/cirurgia , Carcinogênese , Feminino , Humanos , Imuno-Histoquímica , Gordura Intra-Abdominal/química , Gordura Intra-Abdominal/patologia , Antígeno Ki-67/análise , Omento , Inibidor 1 de Ativador de Plasminogênio/análise , Ratos , Ratos Sprague-Dawley , Medição de Risco , Gordura Subcutânea/patologia , Transplante Autólogo/efeitos adversosRESUMO
BACKGROUND AND AIMS: Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity-related complications in the mouse model. To date, SFRP5 expression in non-alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women. MATERIAL AND METHODS: Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral). RESULTS: Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006). CONCLUSION: This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans.