SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Fahad ZadjaliAmilcar Flores-Morales

Abstract

Hepatic steatosis is a prominent feature in patients with growth hormone (GH) deficiency. The ubiquitin ligase SOCS2 attenuates hepatic GH signaling by inhibiting the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) axis. Here, we investigated the role of SOCS2 in the development of diet-induced hepatic steatosis and insulin resistance. SOCS2-knockout (SOCS2(-/-)) mice and wild-type littermates were fed for 4 mo with control or high-fat diet, followed by assessment of insulin sensitivity, hepatic lipid content, and expression of inflammatory cytokines. SOCS2(-/-) mice exhibited increased hepatic TG secretion by 77.6% (P<0.001) as compared with wild-type control mice and were protected from high-fat-diet (HFD)-induced hepatic steatosis, showing 49.3% (P<0.01) reduction in liver TG levels compared to HFD-fed wild-type littermates. In contrast, we found that HFD-triggered attenuation of systemic insulin sensitivity was more marked in SOCS2(-/-) mice. Livers from the HFD-fed SOCS2(-/-) mice showed increased NF-κB activity as well as elevated expression of genes for the inflammatory cytokines IFN-γ and IL-6. An inhibitory role of SOCS2 on Toll-like receptor 4 signaling was demonstrated in macrophage...Continue Reading

References

Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·R StarrW S Alexander
Sep 9, 1999·The New England Journal of Medicine·J TakalaC J Hinds
Apr 25, 2000·Metabolism: Clinical and Experimental·B H GoodpasterD E Kelley
Jul 13, 2000·Nature·D MetcalfW S Alexander
Jul 11, 2002·The Journal of Clinical Endocrinology and Metabolism·Anneli Seppälä-LindroosHannele Yki-Järvinen
Sep 14, 2002·The Journal of Biological Chemistry·Liangyou RuiMorris F White
May 20, 2003·Nature Immunology·Roland LangPeter J Murray
Jul 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kohjiro UekiC Ronald Kahn
Jul 8, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xing Xian YuSanjay Bhanot
Dec 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jörn M SchattenbergMark J Czaja
Jan 18, 2006·Nature Medicine·Fabiana S MachadoJulio Aliberti
Jan 27, 2006·European Journal of Clinical Investigation·P PariniM Rudling
Feb 14, 2006·Molecular Endocrinology·Jessica HarrisChristopher J Ormandy
Oct 31, 2006·Cytokine & Growth Factor Reviews·Elizabeth Rico-BautistaLeandro Fernández-Pérez
Oct 22, 2008·Biochemical and Biophysical Research Communications·Brice EmanuelliC Ronald Kahn
Jan 30, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marcos Martínez-ClementeJoan Clària
Aug 28, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nirupa SachithanandanGregory R Steinberg
Mar 3, 2011·The Journal of Clinical Investigation·Brandon C SosEthan J Weiss
Jun 8, 2011·The Journal of Experimental Medicine·Camille A KnospJames A Johnston
Oct 8, 2011·PloS One·Mattias VesterlundAmilcar Flores-Morales

❮ Previous
Next ❯

Citations

Mar 13, 2014·Progress in Lipid Research·Nishika Sahini, Jürgen Borlak
Oct 10, 2014·International Journal of Molecular Sciences·Arianna SmerieriMaria E Street
Jan 18, 2016·Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición·Leandro Fernández-PérezJuan Carlos Díaz-Chico
Sep 14, 2013·Carcinogenesis·Diego Iglesias-GatoAmilcar Flores-Morales
Sep 24, 2014·Acta Diabetologica·Johanna K DiStefanoGlenn S Gerhard
Aug 15, 2014·Frontiers in Immunology·Heather M Wilson
Jul 5, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Nishika Sahini, Jürgen Borlak
Jun 22, 2013·Acta Biochimica Et Biophysica Sinica·Renfan XuMuxun Zhang
Jan 1, 2012·Pharmaceuticals·Mercedes de Mirecki-GarridoLeandro Fernández-Pérez
Mar 28, 2017·World Journal of Diabetes·Tomoki AbeTakeshi Nikawa
Sep 20, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Janghyun KimJae W Lee
Oct 28, 2019·Mammalian Genome : Official Journal of the International Mammalian Genome Society·H J Abu-Toamih AtamniFuad A Iraqi
Oct 28, 2019·International Journal of Molecular Sciences·Xin LiBin Liu
Jul 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hee Young KimWon-Woo Lee
Nov 20, 2016·Neural Regeneration Research·Harleen S Basrai, Ann M Turnley
Nov 13, 2015·Hormone Molecular Biology and Clinical Investigation·Amira AlkharusiLeandro Fernandez-Pérez
May 1, 2020·International Journal of Molecular Sciences·Amna Al-AraimiFahad Zadjali
Nov 25, 2020·Journal of Translational Medicine·Junfeng YeDi Sun
May 1, 2021·International Journal of Molecular Sciences·Lucie ŠedováRadislav Sedlacek
Nov 9, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eiji MunetsunaShuji Hashimoto

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.