Browsing by Author "Zhang, Shuai"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue
    Zhang, Shuai (Virginia Tech, 2013-12-12)
    The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity.
  • Thumbnail Image
    The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy
    Zhang, Shuai; Zheng, Yilei; Du, Hong; Zhang, Wei; Li, Haohuan; Ou, Yangping; Xu, Funeng; Lin, Juchun; Fu, Hualin; Ni, Xueqing; Chang, Li-Jen; Shu, Gang (MDPI, 2023-06-19)
    The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.
  • Thumbnail Image
    Physiological and Biochemical Aspects of Methionine Isomers and Precursors in Broilers
    Zhang, Shuai (Virginia Tech, 2016-07-19)
    Methionine (Met) is an essential amino acid for animals and also the first limiting amino acid in a broiler diet. The dietary supplemental Met sources include the natural isoform L-methionine (L-Met), the synthetic form DL-methionine (DL-Met) and the synthetic Met precursor DL-2-hydroxy-4 (methylthio)-butanoic acid (DL-HMTBA). The objective of this dissertation was to determine the effect of different dietary Met source supplementation and Met deficiency on a series of physiological and biochemical aspects, including growth performance, global DNA methylation and methyltransferase activity, blood antioxidant profile (e.g., acute phase protein, leukocyte count), intestinal nutrient transporter gene expression, Met converting enzyme gene expression and activity, oxidative stress markers, and a potential pathway related to amino acid signaling. To achieve this goal, male Cobb-500 broilers were raised from day of hatch (d0) to d35 post-hatch and fed a diet deficient in methionine and cysteine (Met + Cys) (control) or the same diet supplemented with 0.22% DL-Met, 0.22% L-Met or 0.31% DL-HMTBA (to provide 0.22% DL-Met equivalent) to meet Met + Cys requirements. Tissues (liver, breast muscle, duodenum, jejunum and ileum) and blood samples were collected at various ages from d0 to d35 for analysis. Met supplementation significantly improved body weight gain and feed efficiency compared to the Met deficient group, but no differences were observed among DL-Met, L-Met and DL-HMTBA for growth performance parameters (P > 0.05). Met supplementation had no effect on red blood cell packed cell volume, white blood cell differential count, hepatic total DNA methylation, DNA methyltransferase and Met oxidase activity, and had limited effects on activation of p70S6K, a key amino acid signaling protein (P > 0.05). Although dietary Met sources did not change oxidative status of the treated chickens, both L-Met and DL-Met but not DL-HMTBA supplementation decreased the level of acute phase protein serum amyloid A compared to the control group (P > 0.05). The effect of Met supplementation on gene expression of nutrient transporters and Met converting enzymes were complex and dynamic. Most of the target genes demonstrated tissue- and development-dependent expression patterns, with few significant treatment effects observed. L-Met and DL-Met but not DL-HMTBA supplementation enhanced the neutral amino acid transporters ATB0,+ and B0AT gene expression in various small intestinal segments. All three Met sources increased monocarboxylic acid transporter (MCT1) gene expression in the jejunum. DL-HMTBA and L-Met fed chickens showed greater hepatic L-HMTBA oxidase (HAO1) gene expression. DL-Met increased glutamic-oxaloacetic transaminase 2 (GOT2) gene expression in the duodenum. An in vitro study with tissue explants, however, did not demonstrate a similar gene expression pattern as that in the in vivo study. Lastly, RNA sequencing results illustrated that Met deficiency could lead to many differentially expressed genes but different supplemental Met sources had no influence on hepatic gene expression profiles. In conclusion, as common dietary supplemental Met sources, L-Met, DL-Met and DL-HMTBA exhibited similarity in impacting intestinal amino acid/peptide/monocarboxylic acid transporter gene expression and Met converting enzyme activity. The regulatory roles of Met as an antioxidant and nutrient signaling in cell metabolism were not affected by different dietary supplemental Met sources.
  • Thumbnail Image
    The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
    Zhang, Shuai; Hulver, Matthew W.; McMillan, Ryan P.; Cline, Mark A.; Gilbert, Elizabeth R. (2014-02-12)
    Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. The ability to alter substrate oxidation in response to nutritional state depends on the genetically influenced balance between oxidation and storage capacities. Competition between fatty acids and glucose for oxidation occurs at the level of the pyruvate dehydrogenase complex (PDC). The PDC is normally active in most tissues in the fed state, and suppressing PDC activity by pyruvate dehydrogenase (PDH) kinase (PDK) is crucial to maintain energy homeostasis under some extreme nutritional conditions in mammals. Conversely, inappropriate suppression of PDC activity might promote the development of metabolic diseases. This review summarizes PDKs’ pivotal role in control of metabolic flexibility under various nutrient conditions and in different tissues, with emphasis on the best characterized PDK4. Understanding the regulation of PDC and PDKs and their roles in energy homeostasis could be beneficial to alleviate metabolic inflexibility and to provide possible therapies for metabolic diseases, including type 2 diabetes (T2D).