White adipose tissue (WAT) lipolysis contributes to energy balance during fasting. Lipolysis can proceed by the sequential hydrolysis of triglycerides (TGs) by adipose triglyceride lipase (ATGL), then of diacylglycerols (DGs) by hormone-sensitive lipase (HSL). We showed that the combined genetic deficiency of ATGL and HSL in mouse adipose tissue produces a striking different phenotype from that of isolated ATGL deficiency, inconsistent with the linear model of lipolysis. We hypothesized that the mechanism might be functional redundancy between ATGL and HSL. To test this, the TG hydrolase activity of HSL was measured in WAT. HSL showed TG hydrolase activity. Then, to test ATGL for activity towards DGs, radiolabeled DGs were incubated with HSL-deficient lipid droplet fractions. The content of TG increased, suggesting DG-to-TG synthesis rather than DG hydrolysis. TG synthesis was abolished by a specific ATGL inhibitor, suggesting that ATGL functions as a transacylase when HSL is deficient, transferring an acyl group from one DG to another, forming a TG plus a monoglyceride (MG) that could be hydrolyzed by monoglyceride lipase. These results reveal a previously unknown physiological redundancy between ATGL and HSL, a mechanism for the epistatic interaction between Pnpla2 and Lipe. It provides an alternative lipolytic pathway, potentially important in patients with deficient lipolysis.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy. K E Y W O R D S cell differentiation, mitochondrial metabolism, TCA cycle | 6689 CHEN Et al.

This study aimed to clarify the relationship between grape (Vitis vinifera L.) quality and environmental factors (climate and soil), and to elucidate the theoretical basis and provide technical guidance for the rational planning of the cultivation area and the precise regulation of the cultivation mode in the future. The fruits of three different grape cultivars, Pinot Noir, Merlot, and Vidal, as well as soil samples and meteorological data were collected from three wine grape growing areas (Wuwei, Zhangye, and Jiayuguan) in the Hexi Corridor, Northwest China. Principal-component analysis (PCA) and correlation analysis were conducted to understand the relationship of grape quality with weather conditions and soil properties. The results showed that the titratable acid content of grape berries was significantly negatively correlated with average temperature from August to September, average minimum temperatures from August to September, and from April to October, mean annual minimum temperature, growing degree days from August to September, and soil total nitrogen content, and significantly positively correlated with average rainfall from April to October, annual mean rainfall, and soil available potassium content. In addition, the pH of grape juice was significantly negatively correlated with annual mean rainfall and soil available potassium content. However, it was significantly positively correlated with average temperature and average minimum temperature from August to September, average minimum temperature from April to October, growing degree days from August to September, as well as soil total nitrogen content. In addition, the results of PCA showed that the fruit quality scores of ‘Vidal’ in Jiayuguan, ‘Merlot’ in Zhangye, and ‘Pinot Noir’ in Wuwei were the highest, respectively. In conclusion, the contents of titratable acid, pH, and Brix° are greatly affected by climate and soil factors. ‘Vidal’, ‘Merlot’, and ‘Pinot Noir’ were suitable for planting in Jiayuguan, Zhangye, and Wuwei, respectively. Nowadays, few reports focus on the relationship between grape quality and soil and climate conditions. Based on the investigation and analysis of the differences of climate, soil, and grape berries quality in the three production areas of Hexi Corridor, the relationship among climate, soil, and grape quality by using statistical methods was studied, which could provide references for clarifying the reasons why environmental factors affect grape quality and select the suitable area for wine grape cultivation.

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