title: Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.
abstract: Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.
authors.affiliation: Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States of America.
authors.forename: Marcella K
authors.initials: MK
authors.lastname: Vaicik
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jill
authors.initials: J
authors.lastname: Thyboll Kortesmaa
authors.affiliation: Center for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Movérare-Skrtic
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kortesmaa
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.affiliation: Center for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Li Yen
authors.initials: LY
authors.lastname: Chong
authors.affiliation: Clinical Research Center and Division of Pathology, Infectious Diseases, Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Rozell
authors.affiliation: Section of Endocrinology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Margo
authors.initials: M
authors.lastname: Emont
authors.affiliation: Section of Endocrinology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Cohen
authors.affiliation: Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States of America; Research Service, Hines Veteran Affairs Hospital, Hines, Illinois, United States of America.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brey
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology*; D052436:Adipose Tissue, White / Q000473:pathology; D000375:Aging / Q000473:pathology; D000818:Animals; D048429:Cell Size; D059305:Diet, High-Fat; D005247:Feeding Behavior; D007797:Laminin / Q000172:deficiency* / Q000378:metabolism; D050155:Lipogenesis; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000473:pathology; D050151:Subcutaneous Fat / Q000473:pathology; D015430:Weight Gain
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin