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Tineke van de Weijer Esther Phielix Lena Bilet Evan G. Williams Eduardo R. Ropelle Alessandra Bierwagen Roshan Livingstone Peter Nowotny Lauren M. Sparks Sabina Paglialunga Julia Szendroedi Bas Havekes Norman Moullan Eija Pirinen Jong-Hee Hwang Vera B. Schrauwen-Hinderling Matthijs K.C. Hesselink Johan Auwerx Michael Roden Patrick Schrauwen 《Diabetes》2015,64(4):1193-1201
Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD+) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD+ precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m2) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD+ levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD+ boosters can also directly affect skeletal muscle mitochondrial function in humans. 相似文献
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Helen Reinhart Camargo Catarino Natália Pereira de Godoy Nayara Kastem Scharlack Lia Mara Grosso Neves Fernanda Oliveira de Gaspari de Gaspi Marcelo Augusto Marreto Esquisatto Maria Esméria Corezola do Amaral Fernanda Aparecida Sampaio Mendonça Gláucia Maria Tech dos Santos 《Lasers in medical science》2015,30(3):1069-1079
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Changing the paradigm of organ utilization from PHS increased‐risk donors: an opportunity whose time has come? 下载免费PDF全文
Lena Sibulesky Imran Javed Jorge D. Reyes Ajit P. Limaye 《Clinical transplantation》2015,29(9):724-727
Approximately 8–11% of all organ donors are classified by Public Health Service (PHS) as increased‐risk. The proportion of PHS increased‐risk donors is on the rise. At the University of Washington Medical Center, in 2014, the proportion of transplants from PHS increased‐risk donors was 28% of liver transplants and 23% of kidney transplants. Nationally, transplant providers have been reluctant to use organs from PHS increased‐risk donors because of concern for transmission of HIV, HCV, or HBV. There is also patient apprehension when these organs are being offered, and thus the discard rate of these otherwise good quality organs is high. Because of the organ shortage, preventing underutilization of such organs is essential. We provide data and considerations that should be used to guide the use of organs from PHS increased‐risk donors. 相似文献