Glucose intolerance and lipid metabolic adaptations in response to intrauterine and postnatal calorie restriction in male adult rats

Meena Garg, Manikkavasagar Thamotharan, Yun Dai, Venu Lagishetty, Aleksey V Matveyenko, W. N Paul Lee, Sherin U. Devaskar

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CONwere heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic β-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-γ, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, β-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-γ, and ACCα. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipidenzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype.

Original languageEnglish (US)
Pages (from-to)102-113
Number of pages12
JournalEndocrinology
Volume154
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology

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