Our laboratory is interested in understanding nutrient partitioning, especially triglyceride (TG) partitioning, and tissue-specific regulation of lipoprotein lipase (LPL), a key enzyme in TG metabolism. After a meal, plasma TG is broken down into fatty acids and glycerol by LPL, which is located within the capillary surrounding adipose tissue. The fatty acids are taken up by the adipose tissue and stored as TG until needed. During a fast, plasma TG is broken down into fatty acids and glycerol by the LPL located within the capillary surrounding muscle. The fatty acids are taken up by the muscle and oxidized for fuel or presumably stored as TG. What determines whether the fatty acids are oxidized or stored in muscle is unknown. However, these processes may play an important role in obesity and insulin resistance.
Recent studies by our laboratory show that adipose tissue LPL activity is reduced and skeletal muscle LPL activity is increased after weight loss and exercise in older, obese, postmenopausal women. Weight loss alone did not affect adipose tissue or skeletal muscle LPL activity, suggesting that exercise in conjunction with weight loss is a better method to â?orealignâ? tissue LPL activity. We have evidence from studies in nonhuman primates that the increase in skeletal muscle LPL activity after PPAR-a agonist treatment is positively associated with the increase in carnitine palmitoyltransferase (CPT) activity. CPT is the mitochondrial enzyme that allows long-chain fatty acids to be oxidized as fuel. In addition, the increase in CPT activity following PPAR-a agonist treatment is positively associated with the increase in glycogen synthase (GS) activity. GS is an important enzyme for glycogen storage. Therefore, we are interested in determining whether the increase in LPL activity following weight loss and exercise in postmenopausal women is associated with an increase in PPAR-a gene expression, an increase in CPT activity and/or an increase in GS activity in skeletal muscle. Our hypothesis is that an intervention that increases PPAR-a gene expression in skeletal muscle will improve fatty acid oxidation and therefore increase LPL activity (lower plasma TG) and increase GS activity (insulin sensitivity).
Most Recent Publications
Ortmeyer HK, MP Sajan, A Miura, Y Kanoh, J Rivas, Y Li, ML Standaert, AS Ryan, NL Bodkin, RV Farese, BC Hansen. Insulin signaling and insulin sensitizing in muscle and liver of obese monkeys: PPARgamma agonist improves defective activation of atypical protein kinase C. Antioxid Redox Signal 14:207-219, 2011.
Huang W, A Metlakunta, N Dedousis, HK Ortmeyer, M Stefanovic-Racic, RM O'Doherty. Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic VLDL Production in Rats, Endocrinology 150: 2169-74, 2009.
Nadeau KJ, LB Ehlers, LE Aguirre, RL Moore, KN Jew, HK Ortmeyer, BC Hansen, JEB Reusch, B Draznin. Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle. Am J Physiol Endocrinol Metab 291:E90-E98, 2006
Ferrara CM, AP Goldberg, HK Ortmeyer and AS Ryan. Effects of aerobic and resistive exercise trainingon glucose disposal and skeletal muscle metabolism in older men. J Gerontol A Biol Sci Med Sci 61A:480-487, 2006.
Ortmeyer HK, Y Adall, KR Marciani, A Katsiaras, AS Ryan, NL Bodkin and BC Hansen. Skeletal muscle glycogen synthase subcellular localization: effects of insulin and PPAR-alpha agonist (K-111) administration in rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 288:R1509-R1517, 2005.
Bodkin NL, TM Alexander, HK Ortmeyer, E Johnson and BC Hansen. Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci 58:212-219, 2003.
Standaert, ML, HK Ortmeyer, MP Sajan, Y Kanoh, G Bandyopadhyay, BC Hansen and RV Farese. Skeletal muscle insulin resistance in obesity-associated type 2 diabetes mellitus in monkeys involves a defect in insulin activation of atypical protein kinase-C. Diabetes 51:2936-2943, 2002.