GSE120429: AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose

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GROUP CONDITION SAMPLES
C57BL/6J mice; Age 16 weeks
GSM3400694 GSM3400695 GSM3400696 GSM3400697 GSM3400698 GSM3400699
GSM3400688 GSM3400689 GSM3400690 GSM3400691 GSM3400692 GSM3400693
C57BL/6J mice; Age 24 weeks
GSM3400706 GSM3400707 GSM3400708 GSM3400709 GSM3400710 GSM3400711
GSM3400700 GSM3400701 GSM3400702 GSM3400703 GSM3400704 GSM3400705
Description

Submission Date: Sep 25, 2018

Summary: Purpose: To investigate alterations in subcutaneous white adipose gene expression induced by genetic AMPK activation in vivo, in mice fed a chow or a high-fat diet.

Methods: Subcutaneous white adipose tissue mRNA profiles of wild-type transgenic (WT-Tg) mice and mice expressing a gain-of-function AMPK mutant gamma1 subunit (D316A-Tg) were generated by deep sequencing.

Results: RNA sequencing revealed over 3000 differentially expressed genes between WT-Tg and D316A-Tg subcutaneous white adipose tissue (WATsc) from mice fed a high fat diet (HFD), of which many were classified as 'skeletal muscle-associated'. Interestingly, uncoupling protein 1 (UCP1), associated with 'beige' adipocyte formation in WATsc, was not differentially expressed. On a chow diet, many differentially expressed genes were also identified, with gene ontology analysis identifiying glycolysis, TCA cycle and brown fat differentiation as highly enriched; key features of brown adipocyte identity. HFD-associated skeletal-muscle associated gene expression was either not significantly altered, or significantly down-regulated on a chow diet, indicating a diet-induced gene signature in D316A-Tg WATsc.

Conclusions: Our study revealed gene signatures indicative of brown adipocyte development on a chow diet, where no overt metabolic phenotype was observed in gain-of-function animals. When fed a HFD, WATsc from D316A-Tg mice displayed a muscle-like gene signature, expressing key components of creatine and calcium thermogenic cycles including Ckmt2 (creatine kinase, mitochondrial 2) Atp2a1 (SERCA1-sarco/endoplasmic reticulum ATPase 1) and ryr1 (ryanodine receptor 1). UCP1 expression was not altered between WT-Tg and D316A-Tg mice fed a HFD. Our findings suggest a novel role for AMPK in the regulation of white adipocyte identity and a potentially novel cell population that, when metabolically challenged, preferrentially utilise muscle-like thermogenic futile cycles independent of UCP1 to mediate whole organism energy expenditure.

GEO Accession ID: GSE120429

PMID: 30887000

Description

Submission Date: Sep 25, 2018

Summary: Purpose: To investigate alterations in subcutaneous white adipose gene expression induced by genetic AMPK activation in vivo, in mice fed a chow or a high-fat diet.

Methods: Subcutaneous white adipose tissue mRNA profiles of wild-type transgenic (WT-Tg) mice and mice expressing a gain-of-function AMPK mutant gamma1 subunit (D316A-Tg) were generated by deep sequencing.

Results: RNA sequencing revealed over 3000 differentially expressed genes between WT-Tg and D316A-Tg subcutaneous white adipose tissue (WATsc) from mice fed a high fat diet (HFD), of which many were classified as 'skeletal muscle-associated'. Interestingly, uncoupling protein 1 (UCP1), associated with 'beige' adipocyte formation in WATsc, was not differentially expressed. On a chow diet, many differentially expressed genes were also identified, with gene ontology analysis identifiying glycolysis, TCA cycle and brown fat differentiation as highly enriched; key features of brown adipocyte identity. HFD-associated skeletal-muscle associated gene expression was either not significantly altered, or significantly down-regulated on a chow diet, indicating a diet-induced gene signature in D316A-Tg WATsc.

Conclusions: Our study revealed gene signatures indicative of brown adipocyte development on a chow diet, where no overt metabolic phenotype was observed in gain-of-function animals. When fed a HFD, WATsc from D316A-Tg mice displayed a muscle-like gene signature, expressing key components of creatine and calcium thermogenic cycles including Ckmt2 (creatine kinase, mitochondrial 2) Atp2a1 (SERCA1-sarco/endoplasmic reticulum ATPase 1) and ryr1 (ryanodine receptor 1). UCP1 expression was not altered between WT-Tg and D316A-Tg mice fed a HFD. Our findings suggest a novel role for AMPK in the regulation of white adipocyte identity and a potentially novel cell population that, when metabolically challenged, preferrentially utilise muscle-like thermogenic futile cycles independent of UCP1 to mediate whole organism energy expenditure.

GEO Accession ID: GSE120429

PMID: 30887000

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