De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health

Nat Commun. 2013;4:1528. doi: 10.1038/ncomms2537.

Abstract

Clinical interest in de novo lipogenesis has been sparked by recent studies in rodents demonstrating that de novo lipogenesis specifically in white adipose tissue produces the insulin-sensitizing fatty acid palmitoleate. By contrast, hepatic lipogenesis is thought to contribute to metabolic disease. How de novo lipogenesis in white adipose tissue versus liver is altered in human obesity and insulin resistance is poorly understood. Here we show that lipogenic enzymes and the glucose transporter-4 are markedly decreased in white adipose tissue of insulin-resistant obese individuals compared with non-obese controls. By contrast, lipogenic enzymes are substantially upregulated in the liver of obese subjects. Bariatric weight loss restored de novo lipogenesis and glucose transporter-4 gene expression in white adipose tissue. Notably, lipogenic gene expression in both white adipose tissue and liver was strongly linked to the expression of carbohydrate-responsive element-binding protein-β and to metabolic risk markers. Thus, de novo lipogenesis predicts metabolic health in humans in a tissue-specific manner and is likely regulated by glucose-dependent carbohydrate-responsive element-binding protein activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity* / genetics
  • Adult
  • Bariatric Surgery
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Body Mass Index
  • Fatty Acid Synthases / metabolism
  • Fatty Acids / metabolism
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Gene Dosage / genetics
  • Gene Expression Regulation
  • Glucose Transporter Type 4 / metabolism
  • Health*
  • Humans
  • Insulin Resistance
  • Intra-Abdominal Fat / metabolism
  • Lipogenesis* / genetics
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / surgery
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Risk Factors
  • Subcutaneous Fat / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Fatty Acids
  • Glucose Transporter Type 4
  • MLXIPL protein, human
  • RNA, Messenger
  • SLC2A4 protein, human
  • Tumor Necrosis Factor-alpha
  • Fatty Acid Synthases