The neonatal period in mammals is characterized by high growth rates and is dominated by skeletal muscle hypertrophy. Low birth weight (LBWT) neonates experience restricted growth and development of skeletal muscle, leading to metabolic perturbations later in life. The overall hypothesis of this dissertation was that in utero disturbances in glucose metabolism and increased energy requirements predisposes LBWT neonatal pigs to metabolic disturbances after birth. We sought to increase growth of skeletal muscle and improve glucose production through increasing dietary energy and to determine the changes in glucose catabolism and metabolic flexibility in different skeletal muscle fiber types in LBWT neonates. Piglets were considered normal birth weight (NBWT) and LBWT when birth weight was within 0.5 SD and below 2 SD of the litter average, respectively. Increasing dietary energy increased lean deposition in the longissimus dorsi (LD) in both NBWT and LBWT neonates. Although glucose rate of appearance was greater in LBWT compared to their NBWT sibling, glucose concentrations were reduced in LBWT compared to NBWT pigs, regardless of diet fed. Postprandial glucose concentrations were lower in LBWT compared to NBWT pigs, regardless of diet fed, although rate of appearance did not differ between them. This would suggest that glucose is being absorbed in the peripheral tissues to be utilized. However, expression of enzymes related to glycolysis were downregulated in both the soleus and LD of LBWT compared to NBWT neonatal pigs. In addition, expression of enzymes related to the catabolism of glucose in the serine biosynthetic pathway were decreased in both the soleus and LD muscles of LBWT compared to NBWT neonatal pigs. Expression of the pentose phosphate pathway was slightly increased in LBWT compared to NBWT siblings in both muscle types. Increased expression of pyruvate dehydrogenase 4 was exhibited in both the soleus and LD of LBWT pigs compared to NBWT siblings. This would indicate a switch in fuel utilization to more fatty acid oxidation. By contrast, CO2 production from the oxidation of palmitate was reduced in LBWT compared with NBWT pigs along with reduced oxidation of glucose and pyruvate. In conclusion, lipid supplementation increased growth at the expense of fat deposition in the liver of NBWT and LBWT pigs. However, supplementing with fat did not increase glucose production due to the contribution of glycerol remaining constant. Hypoglycemia cannot be attributed to greater catabolism in skeletal muscle due to decreased expression of glycolytic genes and the addition of fatty acids did not spare glucose oxidation in skeletal muscle of LBWT pigs. / PHD / During the neonatal period animals display the fastest growth rates, especially pertaining to muscle growth. Muscle development in low birth weight (LBWT) is restricted, leading not only to impaired postnatal growth but increases the risk for developing metabolic diseases later in life such as obesity and type 2 diabetes. LBWT is also characterized by decreased glucose concentrations and decreased body fat content at birth. In the present studies we sought to increase growth and improve glucose production by supplementing with a high energy diet and to compare the changes in glucose catabolism in different skeletal muscle fiber types along with analyzing the ability to switch fuel substrates in LBWT and NBWT neonatal pigs. Increasing dietary energy increased longissimus dorsi (LD) weight as a percentage of bodyweight, regardless of growth status. In addition, during fasting glucose production was higher in LBWT compared to their NBWT siblings, regardless of diet. However, glucose concentration in LBWT were lower compared to NBWT neonatal pigs. Although glucose concentrations were lower in LBWT compared to NBWT pigs after a meal, glucose production rate was unchanged among LBWT and NBWT siblings fed either a high or low energy diet. This suggests that glucose uptake is increased in peripheral tissues of LBWT pigs. However, enzymes related to glycolysis in the LD and soleus of LBWT pigs had lower expression than their NBWT sibling. In addition, the enzyme responsible for the shift in fuel selection, pyruvate dehydrogenase kinase 4 (PDK4) was highly expressed in LBWT compared to NBWT neonatal pigs in both the LD and soleus. This would suggest a switch in glucose oxidation to fatty acid oxidation in the skeletal muscle of LBWT neonatal pigs. However, oxidation of fatty acids in both the soleus and LD of LBWT was reduced compared to NBWT neonatal pigs. In conclusion, lipid supplementation increased growth at the expense of lipid deposition in the liver and did not increase glucose production. Reduced glucose concentrations are not due to greater catabolism in skeletal muscle due to decreased expression of glycolytic genes and the addition of fatty acids did not spare glucose oxidation in the skeletal muscle of LBWT pigs.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/99450 |
| Date | 04 February 2019 |
| Creators | McCauley, Sydney Russelle |
| Contributors | Animal and Poultry Sciences, El-Kadi, Samer Wassim, Johnson, Sally E., Rhoads, Robert P., Frisard, Madlyn I. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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