BACKGROUND/AIMS: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR. METHODS: The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U13C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). RESULTS: HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG. CONCLUSION: The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats.
BACKGROUND/AIMS: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR. METHODS: The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U13C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). RESULTS: HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG. CONCLUSION: The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats.
Authors: Nicolas J Pillon; Scott Frendo-Cumbo; Maya R Jacobson; Zhi Liu; Paul L Milligan; Hai Hoang Bui; Juleen R Zierath; Philip J Bilan; Joseph T Brozinick; Amira Klip Journal: J Lipid Res Date: 2018-05-23 Impact factor: 5.922
Authors: Leigh Goedeke; Jamie Bates; Daniel F Vatner; Rachel J Perry; Ting Wang; Ricardo Ramirez; Li Li; Matthew W Ellis; Dongyan Zhang; Kari E Wong; Carine Beysen; Gary W Cline; Adrian S Ray; Gerald I Shulman Journal: Hepatology Date: 2018-12 Impact factor: 17.425
Authors: Piotr Zabielski; Agnieszka Urszula Błachnio-Zabielska; Beata Wójcik; Adrian Chabowski; Jan Górski Journal: PLoS One Date: 2017-11-02 Impact factor: 3.240
Authors: Ilhame Diboun; Manjunath Ramanjaneya; Lina Ahmed; Mohammed Bashir; Alexandra E Butler; Omar Albagha; Abdul Badi Abou-Samra; Stephen L Atkin; Nayef A Mazloum; Mohamed A Elrayess Journal: Front Endocrinol (Lausanne) Date: 2021-06-15 Impact factor: 5.555