We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mono- and Polyunsaturated Fatty Acids Counter Palmitate-Induced Mitochondrial Dysfunction in Rat Skeletal Muscle Cells.
- Authors
Nisr, Raid B.; Shah, Dinesh S.; Hundal, Harinder S.
- Abstract
Background/Aims: Sustained increases in the circulating concentration of saturated fatty acids (SFAs, e.g. palmitate (PA), as seen during obesity, induces a chronic low grade inflammatory state that has been linked to metabolic dysfunction in tissues such as skeletal muscle that is characterized by disturbances in mitochondrial function and heightened production of reactive oxygen species (ROS). In contrast, monounsaturated (MUFAs, e.g. palmitoleate, PO; oleate, OL) and certain polyunsaturated (PUFAs, e.g. linoleate, LO) fatty acids have been shown to protect against some of the harmful metabolic effects induced by SFAs although it currently remains unknown whether this protection is associated with improved morphological and functional changes in mitochondrial biology and redox status in skeletal muscle cells. The aim of the present study was to investigate this issue. Methods: Rat skeletal (L6) myotubes were subject to sustained 16h incubation with SFAs either alone or in combination with a MUFA (PO, OL) or PUFA (LO) prior to performing subcellular fractionation, immunoblotting, fixed/live cell imaging (for assessment of mitochondrial morphology and ROS) or analysis of real time mitochondrial respiration. Results: Incubation of L6 myotubes with PA or stearate (SFA, C18:0) but not laurate (a medium chain SFA, C12:0) induced a robust increase in proinflammatory NFkB signaling as judged by loss of IkBa and increased expression of IL-6. This heightened SFA-induced proinflammatory tone was associated with increased production of ROS (superoxide and hydrogen peroxide) and significant loss in proteins involved in mitochondrial biogenesis, respiration and morphology (i.e. PGC1α, SDHA, ANT1 and MFN2). Consistent with these changes, PA induced profound fragmentation of the mitochondrial network and a marked reduction in mitochondrial respiratory capacity. These changes were not evident in myotubes incubated with PO, OL or LO alone, and, strikingly, these MUFAs and PUFA not only negated the proinflammatory action of PA, but antagonised the biochemical, morphological and functional changes in mitochondrial biology and ROS production induced in myotubes by the sustained oversupply of PA. Conclusion: Our findings indicate that PO, OL and LO exhibit anti-inflammatory and antioxidant characteristics and, significantly, they can ameliorate SFA-induced disturbances in mitochondrial form and function. These observations may have important nutritional implications in developing strategies that could potentially help limit obesity-induced metabolic dysfunction in tissues such as skeletal muscle.
- Subjects
UNSATURATED fatty acids; MITOCHONDRIAL pathology; RAT physiology; SATURATED fatty acids; OBESITY; SKELETAL muscle; REACTIVE oxygen species
- Publication
Cellular Physiology & Biochemistry (Cell Physiol Biochem Press GmbH & Co. KG), 2020, Vol 54, Issue 5, p975
- ISSN
1015-8987
- Publication type
Article
- DOI
10.33594/000000282