RGD Reference Report - White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice. - Rat Genome Database

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White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice.

Authors: Sakane, Sadatsugu  Hikita, Hayato  Shirai, Kumiko  Myojin, Yuta  Sasaki, Youichi  Kudo, Shinnosuke  Fukumoto, Kenji  Mizutani, Naoki  Tahata, Yuki  Makino, Yuki  Yamada, Ryoko  Kodama, Takahiro  Sakamori, Ryotaro  Tatsumi, Tomohide  Takehara, Tetsuo 
Citation: Sakane S, etal., Cell Mol Gastroenterol Hepatol. 2021;12(5):1683-1699. doi: 10.1016/j.jcmgh.2021.07.008. Epub 2021 Jul 22.
RGD ID: 407445922
Pubmed: PMID:34303881   (View Abstract at PubMed)
PMCID: PMC8551788   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jcmgh.2021.07.008   (Journal Full-text)


BACKGROUND & AIMS: Although nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, the role of adipose tissue in NAFLD is not well-understood. Because autophagy has been reported to be involved in the degradation of lipid droplets, we investigated the role of adipose tissue autophagy in the liver pathogenesis of NAFLD.
METHODS: C57BL/6J mice and adipocyte-specific Atg7-knockout mice (Adipoq-Atg7 KO mice) were fed a high-fat diet (HFD).
RESULTS: HFD feeding for up to 4 months increased both inguinal and epididymal white adipose tissue (iWAT and eWAT, respectively; the former represents subcutaneous fat, and the latter represents visceral fat) in mice. After HFD feeding, autophagy flux in both types of white adipose tissue was increased, and the levels of Rubicon, a negative autophagy regulator, were decreased, suggesting autophagy promotion. Adipoq-Atg7 KO mice exhibited suppressed autophagy in both iWAT and eWAT. Adipocyte-specific Atg7 KO enhanced HFD-induced iWAT hypertrophy. On the other hand, eWAT levels in Adipoq-Atg7 KO mice were increased after 1 month of HFD feeding but decreased after 4 months of HFD feeding compared with those in wild-type controls. Cleaved caspase 3 and JNK pathway protein expression in eWAT was increased without cytokine elevation in Adipoq-Atg7 KO mice fed an HFD compared with wild-type mice fed an HFD. Adipocyte-specific Atg7 KO decreased serum free fatty acid levels and ameliorated HFD-induced steatosis, liver inflammation, and fibrosis.
CONCLUSIONS: Autophagy was enhanced in the white adipose tissues of mice fed an HFD. Autophagy inhibition in white adipose tissues ameliorated the liver pathology of NAFLD via adipose-liver crosstalk.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATG7HumanAlcoholic Fatty Liver amelioratesISOAtg7 (Mus musculus) RGD 
Atg7RatAlcoholic Fatty Liver amelioratesISOAtg7 (Mus musculus) RGD 
Atg7MouseAlcoholic Fatty Liver amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atg7  (autophagy related 7)

Genes (Mus musculus)
Atg7  (autophagy related 7)

Genes (Homo sapiens)
ATG7  (autophagy related 7)


Additional Information