PMID- 34580412
OWN - NLM
STAT- MEDLINE
DCOM- 20211228
LR  - 20211228
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Sep 27
TI  - Distinct mechanisms involving diacylglycerol, ceramides, and inflammation 
      underlie insulin resistance in oxidative and glycolytic muscles from high fat-fed 
      rats.
PG  - 19160
LID - 10.1038/s41598-021-98819-7 [doi]
LID - 19160
AB  - This study investigated whether oxidative and glycolytic rat skeletal muscles 
      respond differently to a high-fat (HF) sucrose-enriched diet with respect to 
      diacylglycerol (DAG) and ceramides accumulation, protein kinase C (PKC) 
      activation, glucose metabolism, and the expression of inflammatory genes. HF diet 
      (8 weeks) suppressed insulin-stimulated glycogen synthesis and glucose oxidation 
      in soleus (Sol), extensor digitorum longus (EDL) and epitrochlearis (Epit) 
      muscles. However, DAG and ceramides levels increased in Sol and EDL, but not in 
      Epit muscles of HF-fed rats. Additionally, membrane-bound PKC-delta and PKC-theta 
      increased in Sol and EDL, whereas in Epit muscles both PKC isoforms were reduced 
      by HF diet. In Epit muscles, HF diet also increased the expression of tumor 
      necrosis factor-alpha (TNF-alpha) receptors (CD40 and FAS), toll-like receptor 4 (TLR4), 
      and nuclear factor kappa light polypeptide gene enhancer in B cells (NF-kB), 
      whereas in Sol and EDL muscles the expression of these inflammatory genes 
      remained unchanged upon HF feeding. In conclusion, HF diet caused DAG and 
      ceramides accumulation, PKC activation, and the induction of inflammatory 
      pathways in a fiber type-specific manner. These findings help explain why 
      oxidative and glycolytic muscles similarly develop insulin resistance, despite 
      major differences in their metabolic characteristics and responsiveness to 
      dietary lipid abundance.
CI  - (c) 2021. The Author(s).
FAU - Jani, Shailee
AU  - Jani S
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada.
FAU - Da Eira, Daniel
AU  - Da Eira D
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada.
FAU - Hadday, Ishvinder
AU  - Hadday I
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada.
FAU - Bikopoulos, George
AU  - Bikopoulos G
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada.
FAU - Mohasses, Arta
AU  - Mohasses A
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada.
FAU - de Pinho, Ricardo A
AU  - de Pinho RA
AD  - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade 
      Catolica Do Parana, Curitiba, Parana, Brazil.
FAU - Ceddia, Rolando B
AU  - Ceddia RB
AD  - Muscle Health Research Center - School of Kinesiology and Health Science, York 
      University, 4700 Keele St, North York, ON, M3J 1P3, Canada. roceddia@yorku.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210927
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (1,2-diacylglycerol)
RN  - 0 (Ceramides)
RN  - 0 (Dietary Sucrose)
RN  - 0 (Diglycerides)
RN  - 0 (Insulin)
SB  - IM
MH  - Animals
MH  - Ceramides/analysis/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Dietary Sucrose/adverse effects
MH  - Diglycerides/analysis/metabolism
MH  - Disease Models, Animal
MH  - Glycolysis/*immunology
MH  - Humans
MH  - Inflammation/diagnosis/immunology/metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance/*immunology
MH  - Male
MH  - Muscle, Skeletal/immunology/*metabolism
MH  - Obesity/etiology/immunology/*metabolism
MH  - Oxidative Stress/immunology
MH  - Rats
PMC - PMC8476522
COIS- The authors declare no competing interests.
EDAT- 2021/09/29 06:00
MHDA- 2021/12/29 06:00
PMCR- 2021/09/27
CRDT- 2021/09/28 06:32
PHST- 2021/06/05 00:00 [received]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/09/28 06:32 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/12/29 06:00 [medline]
PHST- 2021/09/27 00:00 [pmc-release]
AID - 10.1038/s41598-021-98819-7 [pii]
AID - 98819 [pii]
AID - 10.1038/s41598-021-98819-7 [doi]
PST - epublish
SO  - Sci Rep. 2021 Sep 27;11(1):19160. doi: 10.1038/s41598-021-98819-7.