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Diabetologia. 2018 Apr;61(4):932-941. doi: 10.1007/s00125-017-4516-8. Epub 2017 Dec 9.

Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic deterioration in mice.

Author information

1
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC8549, Dallas, TX, 75390-8549, USA.
2
McGaw Medical Center of Northwestern University, Department of Internal Medicine, Chicago, IL, USA.
3
Center for Metabolic and Degenerative Diseases, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
4
Lilly Research Laboratories, Division of Eli Lilly and Company, Indianapolis, IN, USA.
5
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC8549, Dallas, TX, 75390-8549, USA. philipp.scherer@UTSouthwestern.edu.
6
Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA. philipp.scherer@UTSouthwestern.edu.

Abstract

AIM/HYPOTHESIS:

Adiponectin (APN), a circulating hormone secreted by mature adipocytes, has been extensively studied because it has beneficial metabolic effects. While many studies have focused on the congenital loss of APN and its effects on systemic body glucose and lipid metabolism, little is known about the effects triggered by acute loss of APN in the adult mouse. We anticipated that genetically induced acute depletion of APN in adult mice would have a more profound effect on systemic metabolic health than congenital deletion of Adipoq, the gene encoding APN, with its associated potential for adaptive responses that may mask the phenotypes.

METHODS:

Mice carrying loxP-flanked regions of Adipoq were generated and bred to the Adipoq (APN) promoter-driven reverse tetracycline-controlled transactivator (rtTA) (APN-rtTA) gene and a tet-responsive Cre line (TRE-Cre) to achieve acute depletion of APN. Upon acute removal of APN in adult mice, systemic glucose and lipid homeostasis were assessed under basal and insulinopenic conditions.

RESULTS:

The acute depletion of APN results in more severe systemic insulin resistance and hyperlipidaemia than in mice with congenital loss of APN. Furthermore, the acute depletion of APN in adult mice results in a much more dramatic reduction in survival rate, with 50% of inducible knockouts dying in the first 5 days under insulinopenic conditions compared with 0% of congenital Adipoq knockout mice under similar conditions.

CONCLUSIONS/INTERPRETATION:

Acute systemic removal of APN results in a much more negative metabolic phenotype compared with congenital knockout of Adipoq. Specifically, our data demonstrate that acute depletion of APN is especially detrimental to lipid homeostasis, both under basal and insulinopenic conditions. This suggests that compensatory mechanisms exist in congenital knockout mice that offset some of the metabolic actions covered by APN.

KEYWORDS:

Adiponectin; Ceramides; Hyperlipidaemia; Inflammation; Insulinopenia

PMID:
29224189
PMCID:
PMC5844860
DOI:
10.1007/s00125-017-4516-8
[Indexed for MEDLINE]
Free PMC Article

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