Liu, Qiuyue;Gu, Xiaorong;Zhao, Yiqiang;Zhang, Jin;Zhao, Yaofeng;Meng, Qingyong;Xu, Guoheng;Hu, Xiaoxiang;Li, Ning
BMB Reports
/
v.43
no.2
/
pp.97-102
/
2010
Clenbuterol, a $\beta_2$-adrenoceptor agonist, has been proven to be a powerful repartition agent that can decrease fat deposition. Based on results from our previous cDNA microarray experiment of pig clenbuterol administration, a novel up-regulated EST was full-length cloned (4859 bp encoding 1041 amino acids) and found to be the pig homolog of large tumor suppressor 2 (Lats2). We mapped pig Lats2 to chromosome 11p13-14 by using FISH, and western blotting demonstrated that pig Lats2 protein was most abundant in adipose. In Drosophila, Lats2 ortholog was reported as a key component of the Hippo pathway which regulates cell differentiation and growth. Here, we show that pig Lats2 exhibit inverted expression to YAP1, another member of the Hippo pathway which positively regulates cell growth and proliferation, during the differentiation of 3T3-L1 preadipocytes. Our results suggested that Lats2 may involve in Hippo pathway regulating the fat reduction by inhibiting adipocyte differentiation and growth.
Reduced fetal growth is independently associated with increased risk of health problems in later life, particularly type 2 diabetes and cardiovascular diseases. Insulin resistance appears to be a key component underlying these metabolic complications. It is suggested that detrimental fetal environment may program insulin resistance syndrome. An insulin-resistant genotype may also result in both low birth weight and insulin resistance syndrome, and it is likely that the association of low birth weight with insulin resistance is the result of both genetic and environmental factors. Early postnatal rapid catch-up growth is closely related to risk for subsequent metabolic diseases. Fat mass is strikingly reduced in neonates born small for gestational age (SGA), and recent data suggest that insulin resistance seen in catch-up growth is related to the disproportionate catch-up in fat mass compared with lean mass. Endocrine disturbances are also recognized in SGA children, but overt clinical problems are infrequent in childhood. Cognitive impairment is reported in some children born SGA, especially those who do not show catch-up growth, in whom early neurodevelopmental evaluation is required. Breast feeding, also known to be protective against the long-term risk of obesity, may prevent some intellectual impairment in SGA children. Calorie-dense feeding does not seem to be appropriate in SGA infants. We must balance the positive effect of nutrition on neural development against rapid fat deposition and the future risk of insulin resistance.
BACKGROUNG/OBJECTIVES: The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. MATERIALS/METHODS: A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration. Body weight and body fat were measured, and mRNA expression levels of proteins involved in adipocyte differentiation, fat accumulation, fat synthesis, lipolysis, and fat oxidation in adipose tissue and the liver were measured. RESULTS: After experimental diet intake for 8 weeks, body weight was significantly lower in the HFCS group compared to the HF group (P < 0.05), and kidney fat and epididymal fat pad weights were significantly lower in the HFCS group compared to the HF group (P < 0.05). In the HFCS group, CCAAT/enhancer binding protein-${\beta}$, peroxisome proliferator-activated receptor-${\gamma}1$ (PPAR-${\gamma}1$), and PPAR-${\gamma}2$ mRNA expression levels were significantly reduced (P < 0.05) in the epididymal fat pad, whereas cluster of differentiation 36, lipoprotein lipase, acetyl-CoA carboxylase-1, sterol regulatory element binding protein-1c, pyruvate dehydrogenase kinase, isozyme-4, glucose-6-phosphate dehydrogenase, and stearoyl-CoA desaturase-1 mRNA expression levels were significantly decreased in liver and adipose tissues (P < 0.05). In the HFCS group, mRNA expression levels of AMP-activated protein kinase, hormone-sensitive lipase, and carnitine palmitoyltransferase-1 were elevated (P < 0.05). CONCLUSIONS: It can be concluded that high maysin corn silk extract inhibits expression of genes involved in adipocyte differentiation, fat accumulation, and fat synthesis as well as promotes expression of genes involved in lipolysis and fat oxidation, further inhibiting body fat accumulation and body weight elevation in experimental animals.
Sixteen pigs from 2 distinct genetic lines (LGAH and VFIL) obtained after eight generations of divergent selection for high (H) and low (L) lean tissue growth rate with ad-libitum feeding (LGA) and voluntary feed intake (VF1), respectively, were used in this study. The objectives of this investigation were to establish appropriate working conditions for the postheparin plasma lipoprotein lipase (LPL) assay and to study relationships between fat deposition and plasma lipids, very low density lipoprotein (VLDL) lipids, VLDL-subfractions and postheparin plasma LPL activity in growing pigs. Four preliminary experiments were performed to determine the appropriate working conditions for the postheparin plasma LPL assays. Postheparin plasma preincubated with SDS (20-50 mM) at $26^{\circ}C$ for 45 minutes inhibited hepatic lipase activity. A total of $2{\mu}l$ VLDL/assay produced maximum stimulation of LPL activity. Postheparin plasma protein and increasing incubation time contributed an optimum response. LGAH pigs had a significantly higher proportion subtraction 2 than VFIL pigs. No differences were observed in postheparin plasma LPL activity and backfat thickness for two lines of pigs. There were positive correlations between backfat thickness and proportion of subtractions 2 and postheparin plasma LPL activity but the results were not statistically significant. Backfat thickness was not statistically correlated with proportion of subtraction 2 and postheparin plasma LPL activity in a multiple regression analysis. It is believed that the apolipoprotein E, which is present in higher quantities in VLDL-subfraction 2 plays an important role for clearing VLDL triacylglycerol into adipose tissue. LPL activity of pigs can be measured by using postheparin plasma technique. If the relationships of backfat thickness and VLDL-subfraction 2 and postheparin plasma LPL activity can be established, it suggests that these parameters could be used as indicators in selection programmes. Further experiments need to be conducted by using larger sample size and different breed of pigs with greater differences in backfat thicknesses to confirm these trends.
Purpose: Obesity is a serious public health issue for the modern society and is considered a chronic health hazard. There are many surgical and pharmacological approaches to treat obesity. However, various potentially hazardous side effects remain the biggest challenge. Therefore, diets based on foods derived from natural products have gained increasing attention compared to anti-obesity drugs. Recently, research on edible insects as a food source has been a topic of considerable interest in the scientific communities. This study examined the anti-obesity effects of ingesting an edible insect by feeding a high-fat diet (HFD)-induced obese mouse models with a diet containing Tenebrio molitor larvae powder (TMLP). Methods: Six-week-old female C57BL/6J mice were divided into 4 groups according to treatment: 100% normal diet (ND), 100% HFD (HFD), HFD 99% + TMLP 1% (TMLP), and HFD 97% + TMLP 3% (TMLP 3%). TMLP was added to the HFD for 6 weeks for the latter two groups. Results: Compared to the HFD group, mice in the TMLP group showed weight loss, and micro-computed tomographic imaging revealed that the volume of the adipose tissue in the abdominal area also showed significant reduction. After an autopsy, the fat weight was found to be significantly reduced in the TMLP group compared to the HFD group. In addition, the degree of fat cell deposition in the liver tissue and the size of the adipocytes significantly decreased in the TMLP group. Reverse transcription polymerase chain reaction analysis for the mRNA expression of adipogenesis-related genes namely CCAAT-enhancer-binding proteins (C/EBP-β, C/EBP-δ), and fatty acid-binding protein 4 (FABP4) showed that the expression levels of these genes were significantly reduced in the TMLP group compared to the HFD group. Serum leptin level also decreased significantly in the TMLP group in the comparison with the HFD group. In addition, total cholesterol, triglyceride, and glucose levels in mouse serum also decreased in the TMLP group. Conclusion: Taken together, our results showed that TMLP effectively inhibited adipocyte growth and reduced body weight in obese mice.
Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.
Yan, Xiaogang;Zhang, Wei;Cheng, Jianbo;Wang, Runlian;Kleemann, David O.;Zhu, Xiaoping;Jia, Zhihai
Asian-Australasian Journal of Animal Sciences
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v.21
no.6
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pp.853-860
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2008
This experiment was conducted to study the effects of chromium (Cr), dietary crude protein (CP) level and potential interactions between these two factors on growth rate and carcass response, insulin activity and lipid metabolism in lambs. Forty-eight, 9-week-old weaned lambs (Dorper$\times$Small-tail Han sheep, mean initial body weight = $22.96kg{\pm}2.60kg$) were used in a $2{\times}3$ factorial arrangement of supplemental Cr (0 ppb, Cr0; 400 ppb, Cr1; or 800 ppb, Cr2 from chromium yeast) and CP levels (157 g/d to 171 g/d for each animal, LP; or 189 g/d to 209 g/d for each animal, HP). Growth data and blood samples were collected at the beginning and end of the feed trial, after which the lambs were killed. Both Cr additive groups and the HP group increased final weight and average daily gain, especially the Cr1 and HP group (p<0.01). HP increased pelvic fat weight (p<0.05), fat thickness of the 10th rib (p<0.05), longissimus muscle area (p<0.01) and rate of deposition of intramuscular fat (p<0.01). Supplemental Cr decreased the rate of deposition of intramuscular fat (p<0.05). Fasting insulin level and the ratio of insulin to glucose were lower with Cr1 than other groups, but with no significant difference. Glucose concentration was not affected by any treatment. Nonesterified fatty acids increased in the Cr1 (p<0.05) and HP (p<0.05) conditions and there was a significant $Cr{\times}CP$ interaction (p<0.05). Cr1 decreased triglycerides (p<0.05) and total cholesterol (p = 0.151) and HP increased high-density lipoprotein cholesterol (p<0.05). Cr1 decreased lipoprotein lipase activity in subcutaneous adipose tissue (aLPL, p<0.05) and the ratio of aLPL to lipoprotein lipase activity in skeletal muscle (mLPL, p = 0.079). mLPL and hepatic lipase (hHL) were not affected by any treatment. In the present study, Cr had limited effects on growth rate and carcass response, whereas Cr and CP had some notable effects on plasma metabolites and enzyme activities. Cr has a potential effect on energy modulation between lipid and muscle tissue. In addition, few $Cr{\times}CP$ interactions were observed.
Adipose tissue deposited within muscle fibers, known as intramuscular fat (IMF or marbling), is a major determinant of meat quality and thereby affects its economic value. The biological mechanisms that determine IMF content are therefore of interest. In this study, 48 genes involved in the bovine peroxisome proliferator-activated receptor signaling pathway, which is involved in lipid metabolism, were investigated to identify candidate genes associated with IMF in the longissimus dorsi of Hanwoo (Korean cattle). Ten genes, retinoid X receptor alpha, peroxisome proliferator-activated receptor gamma (PPARG), phospholipid transfer protein, stearoyl-CoA desaturase, nuclear receptor subfamily 1 group H member 3, fatty acid binding protein 3 (FABP3), carnitine palmitoyltransferase II, acyl-Coenzyme A dehydrogenase long chain (ACADL), acyl-Coenzyme A oxidase 2 branched chain, and fatty acid binding protein 4, showed significant effects with regard to IMF and were differentially expressed between the low- and high-marbled groups (p<0.05). Analysis of the gene co-expression network based on Pearson's correlation coefficients identified 10 up-regulated genes in the high-marbled group that formed a major cluster. Among these genes, the PPARG-FABP4 gene pair exhibited the strongest correlation in the network. Glycerol kinase was found to play a role in mediating activation of the differentially expressed genes. We categorized the 10 significantly differentially expressed genes into the corresponding downstream pathways and investigated the direct interactive relationships among these genes. We suggest that fatty acid oxidation is the major downstream pathway affecting IMF content. The PPARG/RXRA complex triggers activation of target genes involved in fatty acid oxidation resulting in increased triglyceride formation by ATP production. Our findings highlight candidate genes associated with the IMF content of the loin muscle of Korean cattle and provide insight into the biological mechanisms that determine adipose deposition within muscle.
The effect of conjugated linoleic acid (CLA) isomers esterified in diacylglycerol (DAG)-rich oil on lipid metabolism was investigated. Since dietary DAG has been known to induce the regression of atherosclerosis, CLA-DAG and olive-DAG oils containing similar levels of DAG (51.4~54.2%) were synthesized from olive oil. Hyperlipidemic C57BL/6J mice were then fed high-fat high-cholesterol diets supplemented with these oils (5% each) for 7 wk. The CLA-DAG diet containing 2.1% CLA isomers (0.78% c9,t11-CLA; 1.18% t10,c12-CLA) remarkably increased the levels of total plasma cholesterol and glutamic oxaloacetic transaminase (GOT) along with hepatic cholesterol and triacylglycerol (TAG) contents. Furthermore, the CLA-DAG diet inhibited fat uptake into adipose tissue whereas fat deposition (especially in the liver) was increased, resulting in the development of fatty livers. Hepatic fatty acid composition in the CLA-DAG mice was different from that of the olive-DAG mice, showing higher ratios of C16:1/C16:0 and C18:1/C18:0 in the liver. The activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT) was higher in CLA-DAG mice while plasma lecithin:cholesterol acyltransferase (LCAT) activity and the ferric reducing ability of plasma (FRAP) were lower in CLA-DAG mice compared to the olive-DAG animals. Results of the present study suggest that CLA incorporation into DAG oil could induce atherosclerosis in mice.
Background: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. Methods: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. Results: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. Conclusion: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.
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