Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adipose Tissue, Beige / metabolism*
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Adipose Tissue, Beige / pathology
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Adipose Tissue, Brown / metabolism
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Adipose Tissue, Brown / pathology
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Adiposity*
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Adult Stem Cells / metabolism
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Adult Stem Cells / pathology
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Animals
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Basement Membrane / metabolism
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Basement Membrane / pathology
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Cells, Cultured
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Cold Temperature / adverse effects
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Diet, High-Fat / adverse effects
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Energy Intake
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Energy Metabolism*
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Gene Expression Regulation, Developmental
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Insulin Resistance*
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Laminin / genetics
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Laminin / metabolism*
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Male
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Mice, Knockout
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Obesity / etiology
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Obesity / metabolism*
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Obesity / pathology
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Organ Specificity
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Stress, Physiological
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Subcutaneous Fat / metabolism*
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Subcutaneous Fat / pathology
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Uncoupling Protein 1 / genetics
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Uncoupling Protein 1 / metabolism
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Weight Gain
Substances
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Lama4 protein, mouse
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Laminin
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Uncoupling Protein 1