Work

Restricted Adipogenesis in Hypertrophic Obesity

Year: 2013

Type: article

Abstract: The current global diabetes epidemic is driven byobesity. However, many obese individuals do notdevelop insulin resistance or the metabolic com-plications. Inappropriate expansion of the sub-cutaneous adipose cells leads to hypertrophic obesity characterized by a dysregulated adipose tissue with insulin resistance and inflammation. Here, we discuss the limited expandability of the subcutaneous adipose tissue, which, when exceeded, promotes ectopic fat accumulation and metabolic complications. Hypertrophic obesity is associated with an inability to recruit and differentiate new subcutaneous adipose cells. This is not due to lack of precursor cells but to an inability to induce their commitment and differentiation through inactivation of canonical WNT signaling and allowing bone morphogenetic protein 4 (BMP4) to initiate commitment of precursor cells. TheWNT-inducible secreted protein 2 (WISP2) links WNT and BMP4 signaling. It is highly expressed in early adipogenic precursor cells and inhibits adipogenesis through dual mechanisms; cytosolic WISP2 forms a com-plex with ZNF423, a transcriptional activator of peroxi-some proliferator–activated receptor g (PPARg), and this complex is dissociated by BMP4 allowing ZNF423 to enter the nucleus and initiate PPARg activation. However, WISP2 is also a secreted protein that, through unclear mechanisms, directly inhibits PPARg activation. WISP2 expression in human subcutaneous adipose tissue is associated with hypertrophic obesity, markers of ectopic fat accumulation, and degree of insulin resistance. Thus, WISP2 is a novel secreted adipokine at the cross-road between WNT and BMP4 signaling that can play a crit-ical role for the development of hypertrophic obesity and associated metabolic complications. Identifying the receptor and signaling pathways for WISP2 can open up new avenues for treatment.

Source: Diabetes

DOI: 10.2337/db13-0473

Authors: Birgit Gustafson, Ann Hammarstedt, Shahram Hedjazifar, Ulf Smith

Institution: University of Gothenburg

Language: English

Topic: Adipokines, Inflammation, and Metabolic Diseases

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Torsten Söderbergs Stiftelse, Fredrik och Ingrid Thurings Stiftelse, Vetenskapsrådet