Voluntary feeding induces obesity in broiler breeder hens - collateral effects on cardio- and skelato-muscular functions

• Main Authors: Chung-Yu Chen, 陳中玉
• Other Authors: 陳洵一
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/864kd5

碩士 === 國立中興大學 === 動物科學系所 === 100 === After decades of genetic selection for rapid growth and high feed conversion rate, the modern broilers developed a tendency to overeat and several undesirable defects, including obesity, fatty liver, ascites, and sudden death. In mammals, the mechanisms linking obesity to metabolic syndrome and mellitus diabetes are well studied. Due to the intrinsic differences in physiology of avian species such as natural hyperinsulinemia and insulin insensitivity of peripheral tissues, however, the mechanisms linking obesity to tissue steatosis are poorly studied. In the study, a series of approaches were undertaken to explore the mechanisms linking obesity to cardio- and skelato-muscular dysfunctions. Broiler breeder hens receiving ad libitum or restricted feeding for 7 or 21 days were sacrificed for analyses. Results showed that overfeeding resulted in a temporarily sluggish plasma glucose clearance rate, suggesting transient insulin resistance but followed by compensatory uptake of blood glucose by some certain tissues/organs. In breast muscle, analyses of AMP-activated protein kinase (AMPK), a sensor of cellular energy status suggested that overfeeding suppressed AMPK activation and thereby indicated fuel saturation in the breast muscle of overfed hens. Breast triglyceride content was not affected by ad libitum feeding but carnitine palmitoyl transferase I（CPT1）and diglyceride acyltransferase（DGAT）transcript abundance were promoted, suggesting that accumulated acyl-CoA may be channeled into β-oxidation. Ad libitum feeding also promoted breast sphingomyelin content, but exerted no effects on ceramide content. Increased IL-1β（interleukin-1β）production only temporarily occurred after ad libitum feeding for 7 days. These results suggest that susceptible lipotoxicity is not mediated by ceramide and IL-1β in the breast muscle. Overfeeding also suppressed breast Akt activation and superoxide dismutase （SOD） activity, despite that glutathione/glutathione disulfide rario (GSH/GSSG) was concomitantly decreased, suggesting that excessive fatty acid-induced cytoxicity and susceptible insulin insensitivity are mediated by enhanced β-oxidation and subsequent electron leakage and reactive oxygen species （ROS） production. Similar to the responses of breast muscle, overfeeding promoted AMPK activation, triglyceride content and DGAT expression in leg muscle, but decreased acetyl-CoA carboxylase （ACC）transcript abundance and exerted no effects on CPT1 expression. These results suggest that accumulated fatty acyl-CoA of leg muscle is derived from exogenous origins and DGAT may function as a cytoprotective mechanism to direct the cellular fatty acids away from ceramide de novo synthesis and β-oxidation. Leg muscle sphingomyelin and ceramide content were not affected, but IL-1β production was significantly increased by ad libitum feeding, suggesting that susceptible lipotoxicity in the leg muscle may be operated through proinflammatory IL-1β production. Overfeeding suppressed leg muscle Akt activation and SOD activity, but had no effects on glutathione redox ratios. Therefore, the cause of excessive fatty acid-induced cytoxicity and susceptible insulin insensitivity in the leg muscle may be attributed to perturbations of Akt signaling by IL-1β. Activation of AMPK and Akt and IL-1β production in the heart were not different between overfed and restricted hens. Ad libitum feeding significantly promoted heart ceramide and TG content consistent with upregulation of serine palmitoyl transferase（SPT）, sphingomyelinase（SMase）, ACC, CPT1 and DAG transcript abundance, but exerted no effects on sphingomyelin content. These results suggest that excessive acyl-CoA is channeled into ceramide synthesis and β-oxidation leading to lipotoxicity in the heart of overfed hens. Ad libitum feeding also significantly promoted heart SOD activity and inducible nitric oxide synthase（iNOS）transcription, and glutathione redox ratios were significantly decreased. Furthermore, overfeeding also resulted in a higher fractional heart weight, ventricle hypertrophy, and infiltration of immune cells into the cardiomuscular matrices. These results indicate that increased cellular fatty acid availability causes oxidative pressure and ceramide accumulation in the heart, which in turn may render the progression of lipotoxicity leading to cardiomyocyte dysfunction and steatotic hypertrophy. Taken together, ad libitum feeding induces lipotoxic development and susceptible insulin resistance in the skeletal muscle of broiler hens. However, refusal of excessive fuels in the skeletal muscle may shuttle the fuels to other vulnerary organs such as heart leading to higher insults of oxidative stress and ceramide accumulation, which thereby impair heart functionality and induce steatotic hypertrophy.