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Publication : Adipocyte-Specific Laminin Alpha 4 Deletion Preserves Adipose Tissue Health despite Increasing Adiposity.

First Author  Bailey JL Year  2022
Journal  Biomedicines Volume  10
Issue  9 PubMed ID  36140178
Mgi Jnum  J:342818 Mgi Id  MGI:7438023
Doi  10.3390/biomedicines10092077 Citation  Bailey JL, et al. (2022) Adipocyte-Specific Laminin Alpha 4 Deletion Preserves Adipose Tissue Health despite Increasing Adiposity. Biomedicines 10(9)
abstractText  Laminins are heterotrimeric glycoproteins with structural and functional roles in basement membranes. The predominant laminin alpha chain found in adipocyte basement membranes is laminin alpha4 (LAMA4). Global LAMA4 deletion in mice leads to reduced adiposity and increased energy expenditure, but also results in vascular defects that complicate the interpretation of metabolic data. Here, we describe the generation and initial phenotypic analysis of an adipocyte-specific LAMA4 knockout mouse (Lama4(AKO)). We first performed an in-silico analysis to determine the degree to which laminin alpha4 was expressed in human and murine adipocytes. Next, male Lama4(AKO) and control mice were fed chow or high-fat diets and glucose tolerance was assessed along with serum insulin and leptin levels. Adipocyte area was measured in both epididymal and inguinal white adipose tissue (eWAT and iWAT, respectively), and eWAT was used for RNA-sequencing. We found that laminin alpha4 was highly expressed in human and murine adipocytes. Further, chow-fed Lama4(AKO) mice are like control mice in terms of body weight, body composition, and glucose tolerance, although they have larger eWAT adipocytes and lower insulin levels. High-fat-fed Lama4(AKO) mice are fatter and more glucose tolerant when compared to control mice. Transcriptionally, the eWAT of high-fat fed Lama4(AKO) mice resembles that of chow-fed control mice. We conclude from these findings that adipocyte-specific LAMA4 deletion is protective in an obesogenic environment, even though overall adiposity is increased.
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