Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity.

American Journal of Physiology. Cell Physiology
Toru HosoiKoichiro Ozawa

Abstract

Insensitivity to the antiobesity hormone, leptin, has been suggested to be involved in the pathogenesis of obesity. However, the pathological mechanisms underlying the development of leptin resistance are not well-understood. This study aimed to examine the pathological mechanisms of leptin resistance in obesity. In the present study, we found that 4-hydroxy-2-nonenal (4-HNE), an aldehyde, may be involved in the development of leptin resistance. The SH-SY5Y-Ob-Rb human neuroblastoma cell line, transfected to express the Ob-Rb leptin receptor stably, was treated with 4-HNE, and leptin-induced signal transduction was analyzed. We found that 4-HNE dose- and time-dependently inhibited leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation, a major antiobesity signal of leptin. On the other hand, 4-HNE did not affect tyrosine phosphorylation of broad cellular proteins, suggesting that the inhibitory effect may be selective to leptin signaling. Mechanistically, 4-HNE induced the eukaryotic initiation factor 2α-CCAAT/enhancer-binding protein homologous protein arm of endoplasmic reticulum stress signaling, which may be involved in the pathogenesis of leptin resistance. Overall, these results suggest ...Continue Reading

References

Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·N GhilardiR C Skoda
May 16, 1997·The Journal of Biological Chemistry·Y TakahashiK Chihara
Dec 9, 1997·Neurobiology of Aging·M A LovellW R Markesbery
Jan 24, 1998·The Journal of Biological Chemistry·C BjørbaekJ S Flier
Jun 27, 2000·Diabetes·P J ScarpaceN Tümer
Apr 24, 2002·Developmental Cell·Janice M ZabolotnyBenjamin G Neel
Apr 24, 2002·Developmental Cell·Alan ChengMichel L Tremblay
Oct 31, 2002·Nutrition Reviews·Rudolph L Leibel
Feb 8, 2003·Science·Jeffrey M Friedman
Aug 2, 2003·Molecular Aspects of Medicine·Werner Siems, Tilman Grune
Nov 23, 2005·Chemical Research in Toxicology·James D West, Lawrence J Marnett
Oct 31, 2006·European Journal of Pharmacology·Toru HosoiYasuyuki Nomura
Nov 2, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hong CuiDenise D Belsham
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Jun 14, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ikuroh OhsawaShigeo Ohta
Aug 30, 2008·Molecular Pharmacology·Toru HosoiKoichiro Ozawa
Jan 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marciane MilanskiLício A Velloso
Apr 24, 2009·Journal of Alzheimer's Disease : JAD·Lascelles E Lyn-CookSuzanne M de la Monte
Sep 29, 2009·Clinical Science·Toru Hosoi, Koichiro Ozawa
Jul 30, 2010·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Noriyuki ShibataMakio Kobayashi
Nov 9, 2011·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·C M DoakJ C Seidell

❮ Previous
Next ❯

Citations

Sep 2, 2020·European Journal of Medicinal Chemistry·Antonios KousaxidisAthina Geronikaki

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

ImageJ

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.