Search Results (6)

In adipose tissue, reduced expression of the glycerol channel aquaporin 7 (AQP7) has been associated with increased accumulation of triglyceride. The present study determines the relative protein abundances of lipolytic enzymes, AQP7, and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in paired mesenteric and omental visceral adipose tissue (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) in women with either normal weight or upper-body obesity. No differences in the expression of hormone-sensitive lipase (HSL) or AQP7 were found between the two groups in the four depots. The expression of adipocyte triglyceride lipase (ATGL) and HSL were higher in omental VAT and femoral SAT than in mesenteric VAT in both groups of women. Similarly, AQP7 expression was higher in omental VAT than in mesenteric VAT. The expression of PEPCK-C was lower in omental VAT than in femoral SAT. No correlation between the expression of AQP7 and the mean adipocyte size was observed; however, the expression of PEPCK-C positively correlated with the mean adipocyte size. In conclusion, a depot-specific protein expression pattern was found for ATGL, HSL, AQP7, and PEPCK-C. The expression pattern supports that the regulation of AQP7 protein expression is at least in part linked to the lipolytic rate. Furthermore, the results support that the synthesis of glycerol-3-phosphate via glyceroneogenesis contributes to regulating triglyceride accumulation in white adipose tissue in women. Full article

Boosting NAD⁺ levels are considered a promising means to promote healthy aging and ameliorate dysfunctional metabolism. The expression of CD38, the major NAD⁺-consuming enzyme, is downregulated during thermogenesis in both brown and white adipose tissues (BAT and WAT). Moreover, BAT activation and WAT “browning” were enhanced in Cd38^−/− mice. In this study, the role of CD38 in the liver during thermogenesis was investigated, with the liver being the central organ controlling systemic energy metabolism. Wild-type mice and Cd38^−/− mice were exposed to cold temperatures, and levels of metabolites and enzymes were measured in the livers and plasma. During cold exposure, CD38 expression was downregulated in the liver, as in BAT and WAT, with a concomitant increase in NAD(H) and a marked decrease in NADPH levels. Glucose-6-phosphate dehydrogenase and the malic enzyme, along with enzymes in the glycolytic pathway, were downregulated, which is in line with glucose-6-P being re-directed towards glucose release. In Cd38^−/− mice, the cross-regulation between glycolysis and glucose release was lost, although this did not impair the glucose release from glycogen. Glycerol levels were decreased in the liver from Cd38^−/− animals upon cold exposure, suggesting that glyceroneogenesis, as gluconeogenesis, was not properly activated in the absence of CD38. SIRT3 activity, regulating mitochondrial metabolism, was enhanced by cold exposure, whereas its activity was already high at a warm temperature in Cd38^−/− mice and was not further increased by the cold. Notably, FGF21 and bile acid release was enhanced in the liver of Cd38^−/− mice, which might contribute to enhanced BAT activation in Cd38^−/− mice. These results demonstrate that CD38 inhibition can be suggested as a strategy to boost NAD⁺ and would not negatively affect hepatic functions during thermogenesis. Full article

Ketosis is a common nutritional, metabolic disease during the perinatal period in dairy cows characterized by elevated blood β-hydroxybutyrate (BHBA). In this study, RNA sequencing (RNA-seq) was performed to investigate adaptive changes in adipose tissue during the perinatal period of dairy cows. Blood and tailhead subcutaneous white adipose tissue (sWAT) were obtained from ketotic cows (Ket = 8, BHBA ≥ 1.4 mmol/L) and non-ketotic cows (Nket = 6, BHBA < 1.4 mmol/L) 21 d pre-partum and 10 d post-partum. Compared with pre-partum, decreased lipid synthesis due to down-regulation of PCK1 may be in a strong association with clinical ketosis. Simultaneously, PCK2 was downregulated in the Ket postnatally compared to its expression prenatally, and the expression of PCK2 was 2.7~4.2 times higher than that of PCK1, implying a more severe lipid storage impairment in the Ket. Moreover, compared to pre-partum, the upregulated differentially expressed genes post-partum in the Ket were enriched in the inflammatory response biological process. The higher expression of TNC (tenascin C) in the post-partum Ket relative to the Nket suggested that the adipose tissue of ketotic cows might also be accompanied by tissue fibrosis. Notably, pre-partum CD209 was higher in the Ket than in the Nket, which might be used as a candidate marker for the pre-partum prediction of ketosis. Combined with published gene expression traits, these results suggested that inflammation leads to a more widespread downregulation of the lipid synthesis gene network in adipose tissue in ketotic cows. Additionally, sWAT in post-partum cows with ketosis might also be accompanied by tissue fibrosis which could make the treatment of ketosis more difficult. Full article

Ballooning degeneration of hepatocytes is a major distinguishing histological feature of non-alcoholic steatosis (NASH) progression that can lead to cirrhosis and hepatocellular carcinoma (HCC). In this study, we evaluated the effect of the selective PPARα modulator (SPPARMα) pemafibrate (Pema) and sodium-glucose cotransporter 2 (SGLT2) inhibitor tofogliflozin (Tofo) combination treatment on pathological progression in the liver of a mouse model of NASH (STAM) at two time points (onset of NASH progression and HCC survival). At both time points, the Pema and Tofo combination treatment significantly alleviated hyperglycemia and hypertriglyceridemia. The combination treatment significantly reduced ballooning degeneration of hepatocytes. RNA-seq analysis suggested that Pema and Tofo combination treatment resulted in an increase in glyceroneogenesis, triglyceride (TG) uptake, lipolysis and liberated fatty acids re-esterification into TG, lipid droplet (LD) formation, and Cidea/Cidec ratio along with an increased number and reduced size and area of LDs. In addition, combination treatment reduced expression levels of endoplasmic reticulum stress-related genes (Ire1a, Grp78, Xbp1, and Phlda3). Pema and Tofo treatment significantly improved survival rates and reduced the number of tumors in the liver compared to the NASH control group. These results suggest that SPPARMα and SGLT2 inhibitor combination therapy has therapeutic potential to prevent NASH-HCC progression. Full article

Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease. Full article