Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes

TLDR

CL‑316243 treatment induces multilocular, mitochondria‑rich adipocytes in rat white adipose tissue. The study aimed to determine whether these multilocular cells arise from pre‑existing white adipocytes or from precursor proliferation and to characterize the mitochondria they contain. Most multilocular cells originated from existing white adipocytes that converted from unilocular form, producing mitochondria enriched in UCP3 and low‑level UCP1; a minority (~8%) expressed UCP1, and overall mitochondrial protein in WAT increased tenfold with a distinct protein profile from brown adipose tissue.

Abstract

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.