Browsing by Subject "leucine"
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Item Effects of physical activity levels and nutritional intake on skeletal muscle protein turnover and cellular signaling(2010-03-03) Erin Leigh Glynn; Blake B. Rasmussen; Teresa Davis; Elisabet Børsheim; Elena Volpi; Douglas Paddon-JonesLoss of muscle mass is common in many clinical conditions such as cancer, AIDS, burns and paralysis as well as in aging. Decreased muscle mass can contribute to many other complications and co-morbidities related to diseases, trauma and aging including overall weakness, immobility, increased risk of falls, impaired stress response and metabolic dysfunction. Nutrition and resistance exercise are two readily available and extremely anabolic stimuli for skeletal muscle, though their specific cellular mechanisms remain largely unknown. Studies were designed to examine the mammalian target of rapamycin (mTOR) muscle hypertrophy pathway in conditions of differing physical activity levels, to determine the effects of low and high carbohydrate and insulin levels (combined with essential amino acids) on protein turnover and cellular signaling following resistance exercise, and to investigate similar parameters in response to various combinations of anabolic nutrients. Stable isotopic techniques with arterial/venous catheterization and muscle biopsies, immunoprecipitation and immunoblotting, quantitative real-time PCR and hormone (ELISA) assays were utilized to examine muscle protein turnover, cellular signaling pathways, mRNA expression related to proteins of interest and hormonal responses, respectively. The main findings from these studies were that increased physical activity downregulated the mTOR signaling pathway and decreased inhibitory phosphorylation of insulin receptor substrate 1 (IRS-1). In contrast, mTOR activity may play an important role in paraplegia-induced muscle atrophy as 10 weeks of paraplegia in rats significantly downregulated the mTOR pathway. In humans and compared to modest carbohydrate ingestion, higher amounts of carbohydrate and consequent increases in circulating insulin were unable to further reduce muscle protein breakdown, associated signaling or mRNA expression following a bout of resistance exercise. Similarly, increasing concentrations of leucine may not provide any additional benefit to net protein balance, as has been previously proposed. These studies further our understanding of muscle hypertrophy and atrophy, and begin to provide the scientific data necessary in order to establish evidence-based recommendations for the maintenance of skeletal muscle mass during conditions of muscle wasting.Item Involvement of PFKFB3/iPFK2 in the Effects of Leucine and n-3 PUFA in Adipocytes(2012-02-14) Halim, VeraStudies had shown that leucine supplementation increases insulin sensitivity and it has been studied that n-3 PUFA may have an anti-inflammatory effect in adipocytes. However, the extent to which dietary sources such as leucine and/or n-3 PUFA act through PFKFB3/iPFK2 to suppress adipocyte inflammatory response has not been studied; PFKFB3/iPFK2 is a regulator that links adipocyte metabolism and inflammatory responses. In this study, the involvement of PFKFB3/iPFK2 in the effects of insulin sensitizing and anti-inflammatory effect of leucine and/or n-3 PUFA are explored using cultured 3T3-L1 adipocytes including wild-type cells, PFKFB3-control cells (iPFK2-Ctrl) and PFKFB3-knockdown cells (iPFK2-KD). In iPFK2-Ctrl cells, leucine supplementation appears to have insulin-sensitizing effects through improving p-Akt/Akt insulin signaling, but have no effect on adiponectin expression, and appear to have limited anti-inflammatory effects. n-3 PUFA supplementation appears to have limited effects on both insulin sensitizing and anti-inflammatory effects in iPFK2-Ctrl. In contrast, n-3 PUFA exhibit pro-inflammatory expression in iPFK2-KD. The results of this study support the hypothesis that PFKFB3/iPFK2 is critically involved in insulin-sensitizing effects of leucine. This role of PFKFB3/iPFK2, however, appears to be independent of anti-inflammatory responses. Given this, it is likely that PFKFB3/iPFK2 only account, in part, for the beneficial effects of leucine. n-3 PUFA stimulate PFKFB3/iPFK2 activity in wild-type adipocytes. However, PUFA do not exhibit anti-inflammatory and insulin-sensitizing effects in controls. In contrast, n3-PUFA exhibit proinflammatory effects in iPFK2-KD cells. Taken together, PFKFB3/iPFK2 is involved, at least in part, in the effects of insulin sensitization of leucine and appears to protect adipocytes from inflammatory responses, which could be exacerbated by n-3 PUFA when PFKFB3/iPFK2 is disrupted.