Changrong Ge

The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes

Uncoupling proteins (UCPs) belong to the family of mitochondrial transporter proteins that may uncouple the transport of protons across the inner mitochondrial membrane from electron transport and the synthesis of ATP from ADP, hence generating heat rather than energy. In mammals, more than five family members have been identified, including UCP1, UCP2, UCP3, UCP4 (or BMCP1/UCP5) and UCP5. The UCPs may play an important role in energy homeostasis and have become prominent in the fields of thermogenesis, obesity, diabetes and free‐radical biology and have been considered candidate genes for obesity and insulin resistance. They have been as important potential targets for treatment of aging, degenerative diseases, diabetes and obesity. Recently, a series of studies showed the polymorphisms of UCPs gene association with the fat metabolism, obesity and diabetes. This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans.

The polymorphisms of UCP1 genes associated with fat metabolism, obesity and diabetes

Uncoupling protein 1 (UCP1), a 32-kDa protein located in the inner mitochondrial membrane, is abundant in brown adipose tissue, as a proton transporter in mitochondria inner membrane which uncouples oxidative metabolism from ATP synthesis and dissipates energy through the heat. UCP1 has been reported to play important roles for energy homeostasis in rodents and neonate of larger mammals including human. Recently, numerous candidate genes were searched to determine the genetic factors implicated in the pathogenesis of obesity, related metabolic disorders and diabetes. UCP-1, which plays a major role in thermogenesis, was suggested to be one of the candidates. This review summarizes data supporting the existence of brown adipocytes and the role of UCP1 in energy dissipation in adult humans, and the genetic variety association with the fat metabolism, obesity and diabetes.

Impact of dietary protein on lipid metabolism-related gene expression in porcine adipose tissue.

BackgroundHigh dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism.MethodsSixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18%) or low protein (LP: 14%) diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities.ResultsHP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL), carmitine palmtoyltransferase-1B (CPT-1B), peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte-fatty acid binding proteins (A-FABP) at 60 kg, but reduced their expression at 100 kg.Gene expression and enzyme activity of hormone sensitive lipase (HSL) was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPARγ in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg.ConclusionFat deposition in Wujin pigs fed high dietary protein for 25 weeks was reduced mainly by depression of lipogenic gene expression. The mechanism of lipid transport, lipolysis and oxidation in adipose tissue regulated by dietary protein appeared to be different at 60 kg and 100 kg body weights.

Effect of pu-erh tea on body fat and lipid profiles in rats with diet-induced obesity.

The antiobesity and antihyperlipidaemic effects of pu‐erh tea in rats with high fat diet (HFD)‐induced obesity were investigated. Male Sprague‐Dawley rats were randomly divided into five groups and fed varying diets for an 8‐week period: control diet, HFD, and HFD supplemented with low, moderate or high doses of pu‐erh tea extract (0.5 g, 2 g and 4 g/kg BW/day, respectively). Pu‐erh tea significantly reduced the total body weight and the weight of various adipose pads. Pu‐erh tea administration also significantly lowered plasma total cholesterol, triglyceride concentrations and low‐density lipoprotein‐cholesterol levels in rats with HFD‐induced obesity, but did not affect high‐density lipoprotein‐cholesterol levels. Moreover, pu‐erh tea significantly increased lipoprotein lipase, hepatic lipase and hormone‐sensitive lipase activities in epididymal fat tissue in rats with HFD‐induced obesity. Analysis of real‐time reverse transcription‐polymerase chain reaction results indicated that pu‐erh tea significantly enhanced mRNA levels of hormone‐sensitive lipase in rats with HFD‐induced obesity. These results suggest that pu‐erh tea attenuated visceral fat accumulation and improved hyperlipidemia in a rat model of HFD‐induced obesity. Copyright

Molecular characterization of the encoding regions and tissue expression analyses for three novel porcine genes––HNRPA1, YIPF5 and UB2D2

The complete encoding regions of three porcine genes––heterogeneous nuclear ribonucleoprotein A1 (HNRPA1), YIP1 family member 5 (YIPF5) and ubiquitin-conjugating enzyme E2 D2 (UB2D2) were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR) based on the conserved encoding region information of the mouse or other mammals and the referenced highly homologous pig ESTs of these conserved encoding regions. These three novel porcine genes were assigned to GeneID: 768103, 768112, and 780418. The phylogenetic tree analysis revealed that the swine HNRPA1 has closer genetic relationships with the HNRPA1 of mouse and rhesus monkey, but the swine YIPF5 has a closer genetic relationship with the YIPF5 of cattle and the swine UB2D2 shows an evolutional model different with the UB2D2 of other five species. The tissue expression analysis indicated that the swine HNRPA1 gene was moderately expressed in fat, spleen and kidney, weakly expressed in muscle and lung, and hardly expressed in small intestine, large intestine and liver. The swine YIPF5 gene was moderately expressed in fat and spleen, and hardly expressed in small intestine, large intestine, liver, lung, muscle and kidney. The swine UB2D2 gene was weakly expressed in lung, and hardly expressed in small intestine, large intestine, liver, muscle, fat, spleen and kidney. Our experiment established the primary foundation for further research on these three swine genes.

Expression of lipogenic genes during porcine intramuscular preadipocyte differentiation

Intramuscular fat (IMF) content plays an important role in meat quality. Triglyceride (TG) metabolism in intramuscular adipocytes is strongly associated with the intramuscular fat deposition. To better understand the mechanisms leading to IMF deposition we compared the expression levels of genes related to preadipocyte differentiation and lipogenesis in the intramuscular preadipocytes isolated from the longissimus muscle of Wujin and Landrace pigs. The results showed that the intramuscular preadipocytes could differentiate into mature adipocytes in vitro. Triglyceride content in adipocytes isolated from Wujin pigs was higher than Landrace pigs during the middle and later phases of preadipocyte differentiation. The expression levels of genes related to preadipocyte differentiation such as PPARG and CEBPA showed differential expression between Wujin and Landrace porcine adipocytes during the early stage of differentiation. The expression levels of lipogenic genes such as FASN and SREBF1 were significantly higher in Wujin porcine intramuscular preadipocytes than in Landrace intramuscular preadipocytes at the middle and the later stages of differentiation. This suggests that preadipocyte differentiation and lipogenesis exhibited breed-related scheduling.

Effects of Aqueous Extracts of Raw Pu-erh Tea and Ripened Pu-Erh Tea on Proliferation and Differentiation of 3T3-L1 Preadipocytes

Pu‐erh tea has shown anti‐obesity effects but little is known about its effect on proliferation and differentiation of preadipocytes. This study investigated the effects of the aqueous extracts of raw pu‐erh tea and ripened pu‐erh tea on proliferation and differentiation of murine 3T3‐L1 preadiopocytes. We examined dose and time effects of both aqueous extracts on proliferation of 3T3‐L1 preadipocytes. The contents of triglycerides in cytoplasm and the mRNA expression of critical transcriptional factors involved in differentiation were determined. Cytotoxicity and apoptosis rate of preadipocytes by pu‐erh tea extracts treatment were test for toxic and pro‐apoptotic effects. Both aqueous extracts of pu‐erh tea inhibited the proliferation of 3T3‐L1 preadipocytes at the selected time points. At lower concentration of raw pu‐erh tea extracts (less than 300 µg/ml) and ripened pu‐erh tea extracts (less than 350 µg/ml), no significant cytotoxic and pro‐apoptotic were observed. Ripened pu‐erh tea was more effective with lower IC50 than raw pu‐erh tea. Both extracts suppressed the differentiation and down‐regulated the gene expression of peroxisome proliferator‐activated receptor‐γ and CCAAT/enhancer binding proteins‐α. Therefore, these results indicate that both aqueous extracts of pu‐erh tea can inhibit proliferation and differentiation with ripened pu‐erh tea more potent. Polyphenol rich in both extracts may play a role in the inhibition of proliferation and differentiation of 3T3‐L1 preadipocytes. Copyright

Anti-adipocyte scFv-Fc Antibody Suppresses Subcutaneous Adipose Tissue Development and Affects Lipid Metabolism in Minipigs

Anti-adipocyte monoclonal antibody has been shown to reduce body fat mass in animals. Here, we investigated the effects of an anti-adipocyte antibody (single-chain variable fragment and crystallizable fragment, scFv-Fc) on pig subcutaneous adipose tissue development and lipid metabolism. The scFv-Fc antibody did not alter feed intake or body weight of treated pigs. It suppressed subcutaneous adipose tissue development by reducing the percentage of larger adipocytes, which led to a reduction in body fat mass and subcutaneous adipose tissue thickness. Body fat mass was reduced by reducing triglyceride biosynthesis and promoting triglyceride lipolysis in adipose tissue. There was an increase in lipoprotein lipase mRNA expression in adipose tissue and activity in blood and an enhanced transportation of circulating high-density lipoprotein, low-density lipoprotein, and free fatty acids. Blood concentrations of triglyceride, total cholesterol, glucose, insulin, and adiponectin and mRNA expression of adiponectin in adipose tissue remained unaffected. These findings suggest that anti-adipocyte scFv-Fc antibody may have an application for reducing body fat mass in obese subjects.

cDNA Cloning and Tissue Expression Analyses of the Encoding Regions for Three Novel Porcine Genes- MJD1, CDC42 and NECD

The cDNAs for Machado-Joseph disease protein 1 homolog (MJD1), cell division control protein 42 homolog precursor(CDC42) and necdin (NECD) genes of pig were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR) based on the conserved coding sequence information of the MJD1, CDC42, and NECD genes from mouse and other mammals and the referenced porcine EST sequence information. Tissue expression analysis showed the swine MJD1, CDC42, and NECD genes were obviously differentially expressed in different tissues including muscle, heart, liver, backfat, kidney, lung, small intestine, and large intestine. Our experiment established the primary foundation for further research on these three swine genes.

Biological mechanisms discriminating growth rate and adult body weight phenotypes in two Chinese indigenous chicken breeds

BackgroundIntensive selection has resulted in increased growth rates and muscularity in broiler chickens, in addition to adverse effects, including delayed organ development, sudden death syndrome, and altered metabolic rates. The biological mechanisms underlying selection responses remain largely unknown. Non-artificially-selected indigenous Chinese chicken breeds display a wide variety of phenotypes, including differential growth rate, body weight, and muscularity. The Wuding chicken breed is a fast growing large chicken breed, and the Daweishan mini chicken breed is a slow growing small chicken breed. Together they form an ideal model system to study the biological mechanisms underlying broiler chicken selection responses in a natural system. The objective of this study was to study the biological mechanisms underlying differential phenotypes between the two breeds in muscle and liver tissues, and relate these to the growth rate and body development phenotypes of the two breeds.ResultsThe muscle tissue in the Wuding breed showed higher expression of muscle development genes than muscle tissue in the Daweishan chicken breed. This expression was accompanied by higher expression of acute inflammatory response genes in Wuding chicken than in Daweishan chicken. The muscle tissue of the Daweishan mini chicken breed showed higher expression of genes involved in several metabolic mechanisms including endoplasmic reticulum, protein and lipid metabolism, energy metabolism, as well as specific immune traits than in the Wuding chicken. The liver tissue showed fewer differences between the two breeds. Genes displaying higher expression in the Wuding breed than in the Daweishan breed were not associated with a specific gene network or biological mechanism. Genes highly expressed in the Daweishan mini chicken breed compared to the Wuding breed were enriched for protein metabolism, ABC receptors, signal transduction, and IL6-related mechanisms.ConclusionsWe conclude that faster growth rates and larger body size are related to increased expression of genes involved in muscle development and immune response in muscle, while slower growth rates and smaller body size are related to increased general cellular metabolism. The liver of the Daweishan breed displayed increased expression of metabolic genes.