Inhibition of adipose tissue PPAR? prevents increased adipocyte expansion after lipectomy and exacerbates a glucose-intolerant phenotype.

ABSTRACT:

Objectives

Adipose tissue plays a fundamental role in glucose homeostasis. For example, fat removal (lipectomy, LipX) in lean mice, resulting in a compensatory 50% increase in total fat mass, is associated with significant improvement in glucose tolerance. This study was designed to further examine the link between fat removal, adipose tissue compensation and glucose homeostasis using a peroxisome proliferator-activated receptor ? (PPAR ?; activator of adipogenesis) knockout mouse.

Material and methods

The study involved PPAR? knockout (FKO?) or control mice (CON), subdivided into groups that received LipX or Sham surgery. We reasoned that as the ability of adipose tissue to expand in response to LipX would be compromised in FKO? mice, so would improvements in glucose homeostasis.

Results

In CON mice, LipX increased total adipose depot mass (~60%), adipocyte number (~45%) and changed adipocyte distribution to smaller cells. Glucose tolerance was improved (~30%) in LipX CON mice compared to Shams. In FKO? mice, LipX did not result in any significant changes in adipose depot mass, adipocyte number or distribution. LipX FKO? mice were also characterized by reduction of glucose tolerance (~30%) compared to shams.

Conclusions

Inhibition of adipose tissue PPAR? prevented LipX-induced increases in adipocyte expansion and produced a glucose-intolerant phenotype. These data support the notion that adipose tissue expansion is critical to maintain and/or improvement in glucose homeostasis.

SUBMITTER: Booth AD 

PROVIDER: S-EPMC6529148 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature