title: Carnitine Palmitoyltransferase 1b Deficiency Protects Mice from Diet-Induced Insulin Resistance.
abstract: BACKGROUND
  Carnitine Palmitoyl Transferase 1 (CPT1) is the rate-limiting enzyme governing long-chain fatty acid entry into mitochondria. CPT1 inhibitors have been developed and exhibited beneficial effects against type II diabetes in short-term preclinical animal studies. However, the long-term effects of treatment remain unclear and potential non-specific effects of these CPT1 inhibitors hamper in-depth understanding of the potential molecular mechanisms involved.
  
  
  METHODS
  We investigated the effects of restricting the activity of the muscle isoform CPT1b in mice using heterozygous CPT1b deficient (Cpt1b+/-) and Wild Type (WT) mice fed with a High Fat Diet (HFD) for 22 weeks. Insulin sensitivity was assessed using Glucose Tolerance Test (GTT), insulin tolerance test and hyperinsulinemic euglycemic clamps. We also examined body weight/composition, tissue and systemic metabolism/energetic status, lipid profile, transcript analysis, and changes in insulin signaling pathways.
  
  
  RESULTS
  We found thatCpt1b+/-mice were protected from HFD-induced insulin resistance compared to WT littermates.Cpt1b+/-mice exhibited elevated whole body glucose disposal rate and skeletal muscle glucose uptake. Furthermore,Cpt1b+/-skeletal muscle showed diminishedex vivopalmitate oxidative capacity by ~40% and augmented glucose oxidation capacity by ~50% without overt change in whole body energy metabolism. HFD feedingCpt1b+/-but not WT mice exhibited well-maintained insulin signaling in skeletal muscle, heart, and liver.
  
  
  CONCLUSIONS
  The present study on a genetic model of CPT1b restriction supports the concept that partial CPT1b inhibition is a potential therapeutic strategy.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Teayoun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Johnson
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA ; Department of Anatomy, Guangzhou University of Chinese Medicine, Higher Education Mega Center Campus, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Qinqiang
authors.initials: Q
authors.lastname: Long
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Moore
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, USA.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Sharer
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Nagy
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
authors.affiliation: Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wood
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, USA.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yang
keywords: CPT1b; Fatty acid oxidation; Insulin sensitivity; Skeletal muscle