The Absence of Laminin α4 in Male Mice Results in Enhanced Energy Expenditure and Increased Beige Subcutaneous Adipose Tissue

Endocrinology. 2018 Jan 1;159(1):356-367. doi: 10.1210/en.2017-00186.


Laminin α4 (LAMA4) is located in the extracellular basement membrane that surrounds each individual adipocyte. Here we show that LAMA4 null (Lama4-/-) mice exhibit significantly higher energy expenditure (EE) relative to wild-type (WT) mice at room temperature and when exposed to a cold challenge, despite similar levels of food intake and locomotor activity. The Lama4-/- mice are resistant to age- and diet-induced obesity. Expression of uncoupling protein 1 is higher in subcutaneous white adipose tissue of Lama4-/- mice relative to WT animals on either a chow diet or a high-fat diet. In contrast, uncoupling protein 1 expression was not increased in brown adipose tissue. Lama4-/- mice exhibit significantly improved insulin sensitivity compared with WT mice, suggesting improved metabolic function. Overall, these data provide critical evidence for a role of the basement membrane in EE, weight gain, and systemic insulin sensitivity.

Publication types

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

MeSH terms

  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, Beige / pathology
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, Brown / pathology
  • Adiposity*
  • Adult Stem Cells / metabolism
  • Adult Stem Cells / pathology
  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Cells, Cultured
  • Cold Temperature / adverse effects
  • Diet, High-Fat / adverse effects
  • Energy Intake
  • Energy Metabolism*
  • Gene Expression Regulation, Developmental
  • Insulin Resistance*
  • Laminin / genetics
  • Laminin / metabolism*
  • Male
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / pathology
  • Organ Specificity
  • Stress, Physiological
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / pathology
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism
  • Weight Gain


  • Lama4 protein, mouse
  • Laminin
  • Uncoupling Protein 1