Adipose-specific Lipoprotein Lipase Deficiency More Profoundly Affects Brown Than White Fat Biology

J Biol Chem. 2013 May 17;288(20):14046-58. doi: 10.1074/jbc.M113.469270. Epub 2013 Mar 31.

Abstract

Adipose fat storage is thought to require uptake of circulating triglyceride (TG)-derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects the biology of adipose tissue, we created adipose-specific LpL knock-out (ATLO) mice, and we compared them with whole body LpL knock-out mice rescued with muscle LpL expression (MCK/L0) and wild type (WT) mice. ATLO LpL mRNA and activity were reduced, respectively, 75 and 70% in gonadal adipose tissue (GAT), 90 and 80% in subcutaneous tissue, and 84 and 85% in brown adipose tissue (BAT). ATLO mice had increased plasma TG levels associated with reduced chylomicron TG uptake into BAT and lung. ATLO BAT, but not GAT, had altered TG composition. GAT from MCK/L0 was smaller and contained less polyunsaturated fatty acids in TG, although GAT from ATLO was normal unless LpL was overexpressed in muscle. High fat diet feeding led to less adipose in MCK/L0 mice but TG acyl composition in subcutaneous tissue and BAT reverted to that of WT. Therefore, adipocyte LpL in BAT modulates plasma lipoprotein clearance, and the greater metabolic activity of this depot makes its lipid composition more dependent on LpL-mediated uptake. Loss of adipose LpL reduces fat accumulation only if accompanied by greater LpL activity in muscle. These data support the role of LpL as the "gatekeeper" for tissue lipid distribution.

Keywords: Adipocyte; Fatty Acid; Hypertriglyceridemia; Lipids; Macrophages; Obesity.

Publication types

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

MeSH terms

  • Adipocytes / cytology
  • Adipose Tissue / metabolism*
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Bone Marrow Transplantation
  • Chylomicrons / pharmacokinetics
  • Lipids / chemistry
  • Lipolysis
  • Lipoprotein Lipase / deficiency*
  • Lipoprotein Lipase / genetics*
  • Macrophages / cytology
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Chylomicrons
  • Lipids
  • Triglycerides
  • Lipoprotein Lipase