CoA protects against the deleterious effects of caloric overload in Drosophila.

Journal of Lipid Research
Laura Palanker MusselmanThomas J Baranski

Abstract

We developed a Drosophila model of T2D in which high sugar (HS) feeding leads to insulin resistance. In this model, adipose TG storage is protective against fatty acid toxicity and diabetes. Initial biochemical and gene expression studies suggested that deficiency in CoA might underlie reduced TG synthesis in animals during chronic HS feeding. Focusing on the Drosophila fat body (FB), which is specialized for TG storage and lipolysis, we undertook a series of experiments to test the hypothesis that CoA could protect against the deleterious effects of caloric overload. Quantitative metabolomics revealed a reduction in substrate availability for CoA synthesis in the face of an HS diet. Further reducing CoA synthetic capacity by expressing FB-specific RNAi targeting pantothenate kinase (PK orfumble) or phosphopantothenoylcysteine synthase (PPCS) exacerbated HS-diet-induced accumulation of FFAs. Dietary supplementation with pantothenic acid (vitamin B5, a precursor of CoA) was able to ameliorate HS-diet-induced FFA accumulation and hyperglycemia while increasing TG synthesis. Taken together, our data support a model where free CoA is required to support fatty acid esterification and to protect against the toxicity of HS diets.

References

Dec 1, 1989·The Journal of Nutrition·E D Stein, J M Diamond
Jan 30, 2002·Progress in Lipid Research·Simon Eaton
Sep 15, 2004·Molecular Aspects of Medicine·Rona R Ramsay, Victor A Zammit
Dec 14, 2004·Annals of the New York Academy of Sciences·Daniel W Foster
May 17, 2005·Progress in Lipid Research·Roberta LeonardiSuzanne Jackowski
May 31, 2007·Nature Genetics·Venkateswara R ChintapalliJulian A T Dow
Sep 17, 2008·Biochemical Society Transactions·Chong Yew Tan, Antonio Vidal-Puig
Sep 26, 2008·PLoS Biology·Samuel Virtue, Antonio Vidal-Puig
Jul 9, 2009·Cell Metabolism·Rita T BrookheartJean E Schaffer
Jul 18, 2009·Science·Gary Taubes
Jan 9, 2010·Biochimica Et Biophysica Acta·Sam Virtue, Antonio Vidal-Puig
Jan 12, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·David J FosterConnie C W Hsia
Jan 16, 2010·Methods in Molecular Biology·Nathalie Lepage, Susan Aucoin
Mar 13, 2010·Trends in Endocrinology and Metabolism : TEM·Roger H Unger, Philipp E Scherer
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anil RanaOdy C M Sibon
Sep 30, 2010·Diabetes·Jaswinder K Sethi
Oct 20, 2010·Journal of Cheminformatics·Corey D DehavenKay A Lawton
Jul 2, 2011·Disease Models & Mechanisms·Laura Palanker MusselmanThomas J Baranski
Aug 19, 2011·Current Opinion in Clinical Nutrition and Metabolic Care·Bettina Mittendorfer
Oct 12, 2011·Current Opinion in Clinical Nutrition and Metabolic Care·Robert A McPherson, Gil Hardy
Jul 13, 2012·Canadian Journal of Physiology and Pharmacology·Sushil K Jain
Jan 18, 2013·PLoS Genetics·Jianbo NaRoss Cagan
Jan 29, 2013·The Journal of Biological Chemistry·Laura Palanker MusselmanThomas J Baranski
Feb 12, 2013·American Journal of Physiology. Heart and Circulatory Physiology·David G CotterPeter A Crawford
Sep 11, 2013·The Journal of Clinical Investigation·David J HodsonGuy A Rutter
Dec 21, 2013·PloS One·Manuel MaiAlexander Benedikt Leichtle
Jan 16, 2014·American Journal of Physiology. Endocrinology and Metabolism·Blair E WarrenHélène Lemieux
Mar 13, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A FloegelH Boeing
May 20, 2014·Diabetes Research and Clinical Practice·Xiuying ZhangLinong Ji
Sep 10, 2014·Diabetes, Obesity & Metabolism·B WesselsJ J Prompers
Oct 28, 2014·The Journal of Clinical Investigation·David G CotterPeter A Crawford
Feb 19, 2015·PLoS Genetics·Damien GarridoJacques Montagne
Jul 1, 2015·The Journal of Biological Chemistry·Sarah E MaguireAmita Sehgal

❮ Previous
Next ❯

Citations

Nov 1, 2017·Molecular and Cellular Biology·Laura Palanker MusselmanThomas J Baranski
Mar 1, 2018·Genetics·Laura Palanker MusselmanThomas J Baranski
Jun 2, 2018·BioMed Research International·Jéssica P Álvarez-RendónJuan R Riesgo-Escovar
May 11, 2017·Scientific Reports·Tetsuo YasugiTakashi Nishimura
Jul 8, 2017·Genetics·James E CoxJason M Tennessen
Aug 3, 2018·Scientific Reports·Brandon C ShellMike Grotewiel
Aug 28, 2020·Frontiers in Immunology·Preethi PTina Mukherjee
Mar 9, 2018·The Journal of Experimental Biology·Laura Palanker Musselman, Ronald P Kühnlein
Jan 5, 2020·Journal of Lipid Research·Bryon F TuthillLaura Palanker Musselman
Dec 19, 2019·Scientific Reports·Brooke A ClemmonsPhillip R Myer
Jul 31, 2020·Journal of Insect Physiology·Julia SellinMargret H Bülow
Aug 24, 2021·The Journal of Experimental Biology·Bryon F Tuthill IiLaura Palanker Musselman

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.