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Significance
A beforehand unrecognized function is described for collagen XVIII—a ubiquitous, structurally advanced basement membrane proteoglycan—in supporting preadipocyte differentiation and the upkeep of this differentiated state, and therefore the scale and lipid-clearing/storage capabilities of white adipose tissue depots. Particular lack of medium and lengthy isoforms of this nonfibrillar collagen in mice led to decreased adiposity, ectopic deposition of fats in liver, and elevated very low-density lipoprotein-triglyceride ranges. The discovering of a beforehand unidentified extracellular mechanism contributing to regulate of adipogenesis is anticipated to advertise understanding of the molecular and purposeful bases of human hyperlipidemic syndromes related to fatty liver.
Summary
Differentiating 3T3-L1 fibroblasts into mature adipocytes produced hanging will increase in P2 gene-products and dramatic falls in P1-transcribed mRNA, whereas Wnt3a-induced dedifferentiation of mature adipocytes produced reciprocal adjustments in P1 and P2 transcript ranges. P2-transcript ranges in visceral fats have been positively correlated with serum free fatty acid ranges, suggesting that collagen α1 (XVIII) expression contributes to regulation of adipose tissue metabolism in visceral weight problems. Right here, we assess the operate of the N-terminal, area of unknown operate/frizzled-like sequences distinctive to medium/lengthy collagen XVIII by creating P-specific null mice.
Outcomes
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Right here, we’ve got proven that P2-COL18A1 transcript ranges in visceral however not subcutaneous fats are positively correlated with serum free fatty acid concentrations (Fig. S8), and observe that fatty acid uptake is ∼30% larger in visceral (on a gram to gram foundation) than subcutaneous fats (49). Thus, though further research are required to ascertain whether or not the COL18A1 c.331G > A variant itself (or an allele in linkage disequilibrium) is liable for the triglyceride-lowering impact, from the info offered herein it appears conceivable that COL18A1 variants having a serious deleterious affect on collagen XVIII’s DUF/Fz sequences may trigger atherogenic dyslipidemia and fatty liver, secondary to impaired adipogenesis. We additionally discovered proportionally extra P2-derived COL18A1 RNAs and fewer P1-transcripts in visceral than subcutaneous fats of overweight topics, which—based mostly on the outcomes emanating from our P2-null mice research—counsel that this fats depot comprises extra cells committing to adipogenesis and upkeep of the differentiated state.