CTRP6 rapidly responds to acute nutritional changes, regulating adipose tissue expansion and inflammation in mice

Rotem Lahav, Yulia Haim, Nikhil S. Bhandarkar, Liron Levin, Vered Chalifa-Caspi, Dylan Sarver, Ageline Sahagun, Nitzan Maixner, Barr Kovesh, G. William Wong, Assaf Rudich

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In chronic obesity, activated adipose tissue proinflammatory cascades are tightly linked to metabolic dysfunction. Yet, close temporal analyses of the responses to obesogenic environment such as high-fat feeding (HFF) in susceptible mouse strains question the causal relationship between inflammation and metabolic dysfunction, and/or raises the possibility that certain inflammatory cascades play adaptive/homeostatic, rather than pathogenic roles. Here, we hypothesized that CTRP6, a C1QTNF family member, may constitute an early responder to acute nutritional changes in adipose tissue, with potential physiological roles. Both 3-days high-fat feeding (3dHFF) and acute obesity reversal [2-wk switch to low-fat diet after 8-wk HFF (8wHFF)] already induced marked changes in whole body fuel utilization. Although adipose tissue expression of classical proinflammatory cytokines (Tnf-a, Ccl2, and Il1b) exhibited no, or only minor, change, C1qtnf6 uniquely increased, and decreased, in response to 3dHFF and acute obesity reversal, respectively. CTRP6 knockout (KO) mouse embryonic fibroblasts (MEFs) exhibited increased adipogenic gene expression (Pparg, Fabp4, and Adipoq) and markedly reduced inflammatory genes (Tnf-a, Ccl2, and Il6) compared with wild-type MEFs, and recombinant CTRP6 induced the opposite gene expression signature, as assessed by RNA sequencing. Consistently, 3dHFF of CTRP6-KO mice induced a greater whole body and adipose tissue weight gain compared with wild-type littermates. Collectively, we propose CTRP6 as a gene that rapidly responds to acute changes in caloric intake, acting in acute overnutrition to induce a “physiological inflammatory response” that limits adipose tissue expansion.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume321
Issue number5
DOIs
StatePublished - 1 Nov 2021

Keywords

  • Adipose tissue
  • CTRP
  • Obesity reversal
  • Short-term high fat diet

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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