Perinatal nutrition affects adiposity and skeletal muscle fat metabolism in rats

by Ip, P. M

(Uncorrected OCR) Abstract of thesis entitled ?erinatal Nutrition Affects Adiposity and Skeletal Muscle Fat Metabolism in Rats?Submitted by PM Mona Ip For the degree of Master of Philosophy The University of Hong Kong 2004 In recent decades, the hypothesis of ?etal origins of adult disease?have been proposed and have raised research interests in investigating impacts of early nutrition on growth and development of infants, and its long-term consequence on adult heath. Our study focuses on the long-term effects of early nutrition on adult fat metabolism, especially in skeletal muscles. Epidemiologic studies have shown a relationship between early nutrition and adiposity, weight-related morbidity and mortality in adulthood. Association between abnormal fat metabolism in skeletal muscles and obesity has been reported in human recently. Therefore, it is important to study the consequences of early nutrition on growth and nutrient utilization in skeletal muscle, a major organ which utilizes substrates such as glucose and fatty acids, in order to identify its long-term effect on fat metabolism. We investigated the long-term effects of perinatal undernutrition, early postnatal undernutrition or overnutrition on body fat, intramuscular triglycerides contents, enzyme expressions of 5?AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and gene expressions of fatty acid synthase (FAS) and glucose transporter isoform-4 (GLUT4). Timed pregnant Sprague-Dawley rats were pair-fed standard rat chow 70% of their control counterpart throughout pregnancy and lactation to induce perinatal undernutrition in pups (Gp R). For postnatal under-, normal or over- nutrition, newborn pups were reared in litter sizes of 16 (Gp L), 10 (Gp M) or 4 (Gp S) pups, respectively. Pups were weaned at age 20d to a standard rat chow ad libitum until age 180d. Body composition of pups was measured by the EM-Scan instrument at age 20, 90 and 180d, and their fast and slow muscles were studied. Qualitative differences among groups in intramuscular triglycerides content were evaluated by Oil Red O staining. Immunofluorescence staining was used to quantify enzyme levels of ACC and AMPK, and reverse transcription-polymerase chain reaction was used to determine gene expressions of FAS and GLUT4. Result of our study showed that early nutritional status adversely affects body weight and body fat content in adult pups. Pups subjected to perinatal undernutrition (Gp R) and postnatal undernutrition (Gp L) had decreased body weights and pups subjected to postnatal overnutrition had increased body weights by age 180d. Pups in Gp R and L had increased body fat content by age 180d. However, no observable intramuscular triglycerides storage was found in all groups at all ages. Increased ACC and AMPK levels were shown in adult pups from all 3 experimental groups. Upregulation of FAS gene expressions were observed in pups from Gp R in both fast and slow muscles, in pups from Gp S in fast muscles, and in pups from Gp L in slow muscles. Gene expressions of GLUT4 were upregulated in slow muscles of pups from Gp R, and in fast muscles of pups from Gp L and Gp S. Our data suggests that perinatal and early postnatal nutrition affect body mass and adiposity in adulthood. Although no abnormal fat adiposity in adult skeletal muscles was observed, lipid metabolism in adult skeletal muscles was affected adversely by early nutritional environment.