Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway.

Abstract:

:An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high-fructose corn syrup. In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. Here we demonstrate that a KHK-dependent pathway mediates insulin resistance and inflammatory changes in the visceral fat in response to high fructose. We used mice (males, C57BL/6 background) including littermate wild-type control and mice lacking both isoforms of KHK (KHK-null). Fructose diet induced metabolic syndrome, including visceral obesity, insulin resistance, proinflammatory changes in the visceral fat (production of proinflammatory adipokines and macrophage infiltration), the endoplasmic reticulum stress signaling, and decrease of the high-molecular weight adiponectin followed by decrease in the downstream signaling. KHK-KO mice consuming the same high-fructose diet remained lean, with normal insulin sensitivity and healthy visceral adipose tissue with normal adiponectin function not distinguishable from the control by any of the tested parameters. This study demonstrates that blocking KHK and redirecting fructose metabolism to alternative pathways is an effective way to prevent visceral obesity and insulin resistance induced by high fructose, a widespread component of Western diets.

journal_name

Diabetes

journal_title

Diabetes

authors

Marek G,Pannu V,Shanmugham P,Pancione B,Mascia D,Crosson S,Ishimoto T,Sautin YY

doi

10.2337/db14-0411

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

508-18

issue

2

eissn

0012-1797

issn

1939-327X

pii

db14-0411

journal_volume

64

pub_type

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