ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity.

Abstract:

:Body weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) function, and EE. In mice, Enpp2 was highly expressed in visceral white adipose tissue and BAT and is downregulated in hypertrophied adipocytes/adipose tissue. Enpp2(+/-) mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller body weight gains and less insulin resistance than control mice fed the same diet. BAT was functionally more active and EE was increased in Enpp2-deficient mice. In humans, ENPP2 expression in subcutaneous fat and ENPP2 levels in serum were reduced in obese subjects. Taken together, our results establish ENPP2 as an adipose-derived, secreted enzyme that regulates adipose obesity and systemic metabolism. They also suggest ENPP2 could be a useful therapeutic target for the treatment of metabolic disease.

journal_name

Diabetes

journal_title

Diabetes

authors

Nishimura S,Nagasaki M,Okudaira S,Aoki J,Ohmori T,Ohkawa R,Nakamura K,Igarashi K,Yamashita H,Eto K,Uno K,Hayashi N,Kadowaki T,Komuro I,Yatomi Y,Nagai R

doi

10.2337/db13-1694

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

4154-64

issue

12

eissn

0012-1797

issn

1939-327X

pii

db13-1694

journal_volume

63

pub_type

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