Project description:Despite a variety of seasoning ingredients in diets, little is known about their cooperative effect on animal metabolism. We fed rats a diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same diet without seasonings (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. To assess the mechanisms underlying this phenotype, we conducted transcriptome analyses of the hypothalamic–pituitary axis (HP), liver and white adipose tissue (WAT). Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.
Project description:Despite a variety of seasoning ingredients in diets, little is known about their cooperative effect on animal metabolism. We fed rats a diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same diet without seasonings (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. To assess the mechanisms underlying this phenotype, we conducted transcriptome analyses of the hypothalamic–pituitary axis (HP), liver and white adipose tissue (WAT). Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.
Project description:Despite a variety of seasoning ingredients in diets, little is known about their cooperative effect on animal metabolism. We fed rats a diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same diet without seasonings (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. To assess the mechanisms underlying this phenotype, we conducted transcriptome analyses of the hypothalamic–pituitary axis (HP), liver and white adipose tissue (WAT). Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.
Project description:The circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with global Reverbα deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbαFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERBα regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, ReverbαFlox2-6AdipoCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERBα cistrome with differential gene expression reveals broad control of metabolic processes by REVERBα which is unmasked in the obese state.
Project description:Increasing evidence indicates that parental diet affects the metabolism and health of offspring. It is reported that paternal low-protein diet (pLPD) induces glucose intolerance and the expression of genes involved in cholesterol biosynthesis in mouse offspring liver. The aim of the present study was to determine the effect of a pLPD on gene expression in offspring white adipose tissue (WAT), another important tissue for the regulation of metabolism. RNA-seq analysis indicated that pLPD up- and down-regulated 54 and 274 genes, respectively, in offspring WAT,. The mRNA expression of many genes involved in lipogenesis was down-regulated by pLPD feeding, which may contribute to glucose intolerance. The expression of carbohydrate response element-binding protein β (ChREBP-β), an important lipogenic transcription factor, was also significantly lower in the WAT of pLPD offspring, which may have mediated the down-regulation of the lipogenic genes. By contrast, the LPD did not affect the expression of lipogenic genes in the WAT of the male progenitor, but increased the expression of lipid oxidation genes, suggesting that a LPD reduces WAT mass by activating lipid oxidation, and that LPD may reduce WAT mass using differing mechanisms in parents and offspring. These findings add to our understanding of how paternal diet can regulate metabolism in their offspring.
Project description:We previously reported that a low versus high glycemic index (GI) diet on a high fat (30% kcal fat) background (LGI and HGI, respectively) significantly retarded adverse health effects in C57BL/6J male mice. The LGI diet enhanced whole body insulin sensitivity and repressed high fat diet-induced body and adipose tissue weight gain, resulting in reduced serum leptin and resistin levels (Faseb J 2009; 23: 1092-1101). How white adipose tissue (WAT) is effected is examined in the present study. We characterized the molecular mechanisms underlying the GI-mediated effects in WAT using whole genome transcriptomics technology. We show that a LGI vs. HGI diet mainly exerts its beneficial effects on substrate metabolism, especially insulin signaling of fatty acid metabolism. In addition, cell adhesion and cytoskeleton remodeling showed reduced expression in line with lower WAT mass, but it might also be due to altered insulin sensitivity. An important transcription factor showing enhanced expression is PPARgamma. Furthermore, serum levels of triglycerides, total cholesterol, HDL- and LDL-cholesterol were significantly reduced by a LGI vs. HGI diet, and muscle insulin sensitivity was significantly increased as analyzed by PKB/Akt phosphorylation. Cumulatively, even though these mice were fed a high fat diet, the low versus high GI induced significantly favorable changes in metabolism in WAT. These effects suggest a partial overlap with pharmacological approaches by thiazolidinediones (TZDs) to treat insulin resistance and statins and plantsterols/stanols for hypercholesterolemia. It is therefore tempting to speculate that such a dietary approach might beneficially support pharmacological treatment of insulin resistance or hypercholesterolemia in humans. We analyzed 19 epididymal whie adipose tissue (epiWAT) samples from a 13 week High fat diet, Low glycemic index dietary group (LGI, n=9) versus a High fat diet, High glycemic index dietary group (HGI, n=10) after 13 weeks of feeding wildtype C57BL/6J male adult mice. Of the 19 arrays, we excluded 2 arrays for downstream analysis based on quality control (total final set contains 8 LGI and 9 HGI samples).
Project description:Obesity is associated with multiple metabolic comorbidities and continues to be prevalent in the developed world. It has been repeatedly shown that the distribution, not just amount, of excess white adipose tissue (WAT) in obesity correlates with a person’s risk for coronary artery disease and type 2 diabetes. Thus, understanding depot specific mechanisms of WAT development could shed light on mechanisms of metabolic disease. SNPs near the gene CEBPA, which encodes the transcription factor CCAAT/enhancer binding protein alpha (C/EBPa), have been associated by human genome-wide association studies with waist-to-hip ratio, suggesting CEBPA plays depot-specific roles in WAT. C/EBPa is a master regulator of adipocyte differentiation and metabolism, but its role in the development of specific WAT depots is not well understood. We generated mice with AdipoQ-Cre-driven adipocyte-specific Cebpa knockout (Cebpa_ASKO) and found that these mice have drastically reduced gonadal WAT (gWAT) mass. Meanwhile, inguinal WAT (iWAT) develops and is present in normal amounts. However, there are fewer and larger iWAT adipocytes and evidence of altered lipid metabolism, and Cebpa_ASKO mice fail to expand any of their white adipose depots when challenged with a high fat diet. Cebpa_ASKO mice also have multiple other metabolic phenotypes, including hypertrophic, lipid-laden BAT, increased hepatic triglycerides, and increased plasma cholesterol, and each phenotype worsens with prolonged high fat diet feeding. Taken together, these data point to C/EBPa playing depot-specific roles in adipose tissue development, as well as the importance of C/EBPa and visceral adipose tissue in maintaining metabolic homeostasis.