Vimentin is required for normal accumulation of body fat

Abstract

Intermediate filaments (nanofilaments) have many functions, especially in response to cellular stress. Mice lacking vimentin (Vim−/−) display phenotypes reflecting reduced levels of cell activation and ability to counteract stress, for example, decreased reactivity of astrocytes after neurotrauma, decreased migration of astrocytes and fibroblasts, attenuated inflammation and fibrosis in lung injury, delayed wound healing, impaired vascular adaptation to nephrectomy, impaired transendothelial migration of lymphocytes and attenuated atherosclerosis. To address the role of vimentin in fat accumulation, we assessed the body weight and fat by dual-energy X-ray absorptiometry (DEXA) in Vim−/− and matched wildtype (WT) mice. While the weight of 1.5-month-old Vim−/− and WT mice was comparable, Vim−/− mice showed decreased body weight at 3.5, 5.5 and 8.5 months (males by 19–22%, females by 18–29%). At 8.5 months, Vim−/− males and females had less body fat compared to WT mice (a decrease by 24%, p < 0.05, and 33%, p < 0.0001, respectively). The body mass index in 8.5 months old Vim−/− mice was lower in males (6.8 vs. 7.8, p < 0.005) and females (6.0 vs. 7.7, p < 0.0001) despite the slightly lower body length of Vim−/− mice. Increased mortality was observed in adult Vim−/− males. We conclude that vimentin is required for the normal accumulation of body fat.

A dominant vimentin variant causes a rare syndrome with premature aging

“…Our in vitro data were further confirmed by direct observation of lipid distribution defects in zebrafish (Fig. 6e, f ), which is reminiscent of the fat accumulation defects observed in vimentin KO mice [ 8 ]. The increase in lipodystrophy upon injection of wt vimentin mRNA is compatible with the notion that transgenic overexpression of wt vimentin caused pathological anomalies in mice [ 34 ].…”

“…This organ-specific disease was surprising, considering the wide tissue expression of vimentin. In line with this unexpected phenotype, the targeted deletion of vimentin in mice caused widespread but mild phenotypes in unchallenged animals [ 2 , 8 ]. Most recently, the analysis of phospho-deficient vimentin knockin mice indicated a role of vimentin in skin aging, neuronal differentiation, and subcutaneous fat loss [ 9 – 11 ].…”

Peer Review #2 of "Genomic analyses provide insights into breed-of-origin effects from purebreds on three-way crossbred pigs (v0.2)"

“…In adipose, the top 3 significant GO pathways of ASE genes include 'fatty acid metabolic process' (P = 7.24×10 -9 ), 'acylglycerol metabolic process' (P = 6.31×10 -8 ) and 'regulation of cholesterol metabolic process' (P = 8.13×10 -7 ) (Supplementary Figure S9A, Manuscript to be reviewed metabolism of long-chain fatty acids and has been proved to have a close relationship with carcass back fat thickness and intramuscular fat contents (Cho et al, 2011). VIM encodes a type III intermediate filament protein and is required for the normal accumulation of body fat (Wilhelmsson et al, 2019). ACSL1 encodes an isozyme of the long-chain fatty-acid-coenzyme A ligase family and functions in converting free long-chain fatty acids into fatty acyl-CoA esters; a previous study suggested this gene might contribute to the capacity of fat deposition and meat quality in pig breeds (Li et al, 2012).…”

Vimentin Deficiency Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

“…These in vitro studies support the hypothesis that vimentin is involved in obesity and type 2 diabetes mellitus. A recent study reported that vimentin-null mice on a chow diet have lower body weight and less body fat com-pared with wild-type mice, suggesting a role of vimentin in normal accumulation of body fat [9]. However, there have been no animal studies verifying the role of vimentin in highfat diet (HFD)-induced obesity and type 2 diabetes mellitus.…”