The Adipose Tissue Phenotype of Hormone-Sensitive Lipase Deficiency in Mice

Obes Res. 2001 Feb;9(2):119-28. doi: 10.1038/oby.2001.15.

Abstract

Objective: To directly ascertain the physiological roles in adipocytes of hormone-sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can mediate triacylglycerol cleavage in adipocytes.

Research methods and procedures: We performed constitutive gene targeting of the mouse HSL gene (Lipe), subsequently studied the adipose tissue phenotype clinically and histologically, and measured lipolysis in isolated adipocytes.

Results: Homozygous HSL-/- mice have no detectable HSL peptide or cholesteryl esterase activity in adipose tissue, and heterozygous mice have intermediate levels with respect to wild-type and deficient littermates. HSL-deficient mice have normal body weight but reduced abdominal fat mass compared with normal littermates. Histologically, both white and brown adipose tissues in HSL-/- mice show marked heterogeneity in cell size, with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In isolated HSL-/- adipocytes, lipolysis is not significantly increased by beta3-adrenergic stimulation, but under basal conditions in the absence of added catecholamines, the lipolytic rate of isolated HSL-/- adipocytes is at least as high as that of cells from normal controls. Cold tolerance during a 48-hour period at 4 degrees C was similar in HSL-/- mice and controls. Overnight fasting was well-tolerated clinically by HSL-/- mice, but after fasting, liver triglyceride content was significantly lower in HSL-/- mice compared with wild-type controls.

Conclusions: In isolated fat cells, the lipolytic rate after beta-adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL-/- adipocytes suggests that HSL-independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / enzymology
  • Adipose Tissue / enzymology*
  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Blotting, Western
  • Chimera / genetics
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Targeting
  • Genetic Vectors / chemistry
  • Lipolysis / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organ Size
  • Polymerase Chain Reaction
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Sterol Esterase / deficiency*
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism

Substances

  • RNA, Messenger
  • Sterol Esterase