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.

Brown and beige adipose tissues have a significant capacity for energy expenditure that may be exploited as a treatment for obesity and metabolic disease. However, the limited volumes of these tissues in adults hinders realization of this potential. Engineering beige adipose tissue may provide an alternative source of this tissue. In this paper we describe the preparation of poly(ethylene glycol) (PEGDA) hydrogels with mechanical properties similar to native adipose tissue. Adipose derived stem cells (ASC) were cultured in hydrogels without adhesive sequences or degradable monomers. Cells were able to differentiate, independent of scaffold properties and were maintained as a viable and functioning adipose tissue mass. The cells expressed their own basement membrane proteins consistent with the composition of adipose tissue. The ASCs could be induced to express uncoupling protein-1 (UCP-1) and cIDEA, makers of beige adipocytes with expression level varying with hydrogel stiffness. This hydrogel-based culture system serves as a first step in engineering beige adipose tissue.