PMID- 25483313 OWN - NLM STAT- MEDLINE DCOM- 20150918 LR - 20150120 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 26 IP - 2 DP - 2015 Feb TI - Skeletal muscle Sirt3 expression and mitochondrial respiration are regulated by a prenatal low-protein diet. PG - 184-9 LID - S0955-2863(14)00221-6 [pii] LID - 10.1016/j.jnutbio.2014.10.003 [doi] AB - Malnutrition during the fetal growth period increases risk for later obesity and type 2 diabetes mellitus (T2DM). We have shown that a prenatal low-protein (8% protein; LP) diet followed by postnatal high-fat (45% fat; HF) diet results in offspring propensity for adipose tissue catch-up growth, obesity and T2DM in Sprague-Dawley rats. Skeletal muscle is the major tissue for insulin-mediated glucose uptake. Dysfunctional skeletal muscle mitochondrial function, particularly reduction in expression of mitochondrial protein sirtuin protein 3 (Sirt3) contributes to development of T2DM by reducing mitochondrial respiration. Therefore, we hypothesized that maternal LP and postnatal HF diets would increase T2DM risk due to Sirt3 dysfunction within skeletal muscle mitochondria. Using our maternal LP and postnatal HF diet model, we showed that skeletal muscle mitochondrial oxygen consumption rate was decreased by maternal LP diet. Mitochondria copy number, mitochondrial thermogenesis (UCP-1) expression and mitochondrial biogenic factors including nuclear respiratory factor 1 and cytochrome c oxidases 1 and 4 were unaffected by maternal LP and postnatal HF diets. Skeletal muscle Sirt3 mRNA decreased with maternal LP diet. A mitochondrial substrate of Sirt3, succinate dehydrogenase (SDH), is regulated by Sirt3 via lysine residue acetylation status of SDH. Acetylated SDH protein (inactive form) levels were moderately decreased by maternal LP diet. Taken together, these data suggest that maternal LP and postnatal HF diets may increase the risk for T2D by decreasing skeletal muscle oxidative respiration via increased Sirt3 and possibly by decreased amounts of the active form of SDH enzyme. CI - Published by Elsevier Inc. FAU - Claycombe, Kate J AU - Claycombe KJ AD - USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. Electronic address: kate.claycombe@ars.usda.gov. FAU - Roemmich, James N AU - Roemmich JN AD - USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. FAU - Johnson, LuAnn AU - Johnson L AD - USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. FAU - Vomhof-DeKrey, Emilie E AU - Vomhof-DeKrey EE AD - USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. FAU - Johnson, W Thomas AU - Johnson WT AD - USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141114 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Protein Subunits) RN - EC 1.3.99.1 (Succinate Dehydrogenase) RN - EC 3.5.1.- (Sirtuin 3) SB - IM MH - Acetylation MH - Animals MH - Animals, Newborn MH - Diabetes Mellitus, Type 2/etiology/metabolism/pathology MH - Diet, High-Fat/adverse effects MH - Diet, Protein-Restricted/*adverse effects MH - Disease Susceptibility MH - Down-Regulation MH - Female MH - *Gene Expression Regulation, Developmental MH - Male MH - *Maternal Nutritional Physiological Phenomena MH - Mitochondria, Muscle/enzymology/*metabolism/pathology MH - Muscle, Skeletal/growth & development/*metabolism/pathology MH - Pregnancy MH - Protein Processing, Post-Translational MH - Protein Subunits/metabolism MH - Rats, Sprague-Dawley MH - Sirtuin 3/genetics/*metabolism MH - Succinate Dehydrogenase/*metabolism OTO - NOTNLM OT - Maternal low-protein diet OT - Mitochondria OT - SDH OT - SIRT3 OT - Skeletal muscle respiration EDAT- 2014/12/09 06:00 MHDA- 2015/09/19 06:00 CRDT- 2014/12/09 06:00 PHST- 2014/06/20 00:00 [received] PHST- 2014/10/01 00:00 [revised] PHST- 2014/10/02 00:00 [accepted] PHST- 2014/12/09 06:00 [entrez] PHST- 2014/12/09 06:00 [pubmed] PHST- 2015/09/19 06:00 [medline] AID - S0955-2863(14)00221-6 [pii] AID - 10.1016/j.jnutbio.2014.10.003 [doi] PST - ppublish SO - J Nutr Biochem. 2015 Feb;26(2):184-9. doi: 10.1016/j.jnutbio.2014.10.003. Epub 2014 Nov 14.