Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance

Autor: Nicola A, Talbot, Caroline P, Wheeler-Jones, Mark E, Cleasby
Rok vydání: 2014
Předmět:
Macrophage
palm
palmitate
Palmitic Acid
Skeletal muscle
RIPA
radioimmunoprecipitation
CXCL2
Chemokine (C-X-C motif) ligand 2
SDS-PAGE
sodium dodecyl sulphate
polyacrylamide gel electrophoresis
p38 Mitogen-Activated Protein Kinases
JNK
C-jun n-terminal kinase
Fatty Acids
Monounsaturated
Myoblasts
IKK
inhibitor κ kinase
IR
insulin resistance
GSK
glycogen synthase kinase
Cells
Cultured
ANOVA
analysis of variance
AS160
Akt substrate of 160 kDa
IRS1
insulin receptor substrate-1
PMA
phorbol myristate acetate
GLUT
glucose transporter
ERK
extracellular signal-related kinase
FBS
foetal bovine serum
iNOS
inducible nitric oxide synthase
LPS
lipopolysaccharide
Electrophoresis
Polyacrylamide Gel
TLR
Toll-like Receptor
NFκB
nuclear factor-κB
p38 Mitogen-activated protein kinase
SFA
saturated fatty acid
PBS
phosphate-buffered saline
Tumour necrosis factor-α
Enzyme-Linked Immunosorbent Assay
T2D
type 2 diabetes
Real-Time Polymerase Chain Reaction
Article
CM
conditioned medium
mac
macrophage
PKC
protein kinase C
Humans
TNFα
tumour necrosis factor-α
UFA
unsaturated fatty acid
Muscle
Skeletal
FA
fatty acid
IκBα
inhibitor κBα
Insulin resistance
Macrophage Activation
Fatty acid
IL
interleukin
DMEM
Dulbecco’s modified Eagle's medium
siRNA
small interfering RNA
DMSO
dimethylsulphoxide
ABAF
anti-bacterial
anti-fungal
PI3K
phosphoinositol 3-kinase
MCP1
monocyte chemoattractant protein
BSA
bovine serum albumin
MAPK
mitogen-activated protein kinase
Zdroj: Molecular and Cellular Endocrinology
ISSN: 1872-8057
Popis: Highlights • Palmitate-treated macrophage-conditioned medium causes myotube insulin resistance. • This involves activation of myotube p38 mitogen activated protein kinase. • Conditioned medium effects are mediated by tumour necrosis factor-α. • These effects are prevented by addition of palmitoleate. • Palmitoleate treatment of macrophages is insulin sensitising for myotubes.
Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.
Databáze: OpenAIRE
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