Genetic ablation of phosphatidylcholine transfer protein/StarD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure

Metabolism. 2017 Mar;68:145-149. doi: 10.1016/j.metabol.2016.11.012. Epub 2016 Dec 1.

Abstract

Objective: Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is highly expressed in liver and oxidative tissues. PC-TP promotes hepatic glucose production during fasting and aggravates glucose intolerance in high fat fed mice. However, because PC-TP also suppresses thermogenesis in brown adipose tissue (BAT), its direct contribution to obesity-associated diabetes in mice remains unclear. Here we examined the effects of genetic PC-TP ablation on glucose homeostasis in leptin-deficient ob/ob mice, which exhibit both diabetes and altered thermoregulation.

Animals/methods: Mice lacking both PC-TP and leptin (Pctp-/-;ob/ob) were prepared by crossing Pctp-/- with ob/+ mice. Glucose homeostasis was assessed by standard assays, and energy expenditure was determined by indirect calorimetry using a comprehensive laboratory animal monitoring system, which also recorded physical activity and food intake. Body composition was determined by NMR and hepatic lipids by enzymatic assays. Core body temperature was measured using a rectal thermocouple probe.

Results: Pctp-/-;ob/ob mice demonstrated improved glucose homeostasis, as evidenced by markedly improved glucose and pyruvate tolerance tests, without changes in insulin tolerance. However, there were no differences in EE at any ambient temperature. There were also no effects of PC-TP expression on physical activity, food intake or core body temperature.

Conclusions: Improved glucose tolerance in Pctp-/-;ob/ob mice in the absence of increases in energy expenditure or core body temperature indicates a direct pathogenic role for PC-TP in diabetes in leptin deficient mice.

Keywords: Diabetes; Insulin resistance; Leptin; Thermoregulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Composition / genetics
  • Body Temperature / genetics
  • Calorimetry, Indirect
  • Eating
  • Energy Metabolism / genetics*
  • Glucose Intolerance / genetics*
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Homeostasis
  • Insulin Resistance / genetics
  • Leptin / deficiency
  • Leptin / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phospholipid Transfer Proteins / genetics*
  • Phospholipid Transfer Proteins / metabolism*
  • Pyruvates / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7 / genetics

Substances

  • Leptin
  • Phospholipid Transfer Proteins
  • Pyruvates
  • Ptprr protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7