Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.
Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.
Khan
Tayeba
T
Department of Cell Biology, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Muise
Eric S
ES
Iyengar
Puneeth
P
Wang
Zhao V
ZV
Chandalia
Manisha
M
Abate
Nicola
N
Zhang
Bei B
BB
Bonaldo
Paolo
P
Chua
Streamson
S
Scherer
Philipp E
PE
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000375:Aging / Q000502:physiology; D000818:Animals; D048429:Cell Size; D024142:Collagen Type VI / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000473:pathology; D004731:Endotoxins; D005109:Extracellular Matrix / Q000502:physiology*; D005355:Fibrosis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010179:Pancreas / Q000473:pathology
D024142:Collagen Type VI; D004731:Endotoxins; D007328:Insulin; D005947:Glucose