title: A pilot study examining the impact of exercise training on skeletal muscle genes related to the TLR signaling pathway in older adults following hip fracture recovery.
abstract: Older adults after hip fracture surgery experience progressive muscle atrophy and weakness, limiting full recovery. Further understanding of the molecular mechanisms in muscle with adaptation to exercise training in this vulnerable population is necessary. Therefore, we conducted a pilot study to investigate the skeletal muscle inflammatory and ceramide biosynthesis gene expression levels associated with the toll-like receptor (TLR) pathway before (Pre) and following a 3-mo multicomponent exercise training program in older adults (3M, 4F; 78.4 ± 13.3 yr; 25.5 ± 2.3 kg/m2) ~4 mo after repair from hip fracture (HipFx). Vastus lateralis biopsies from the surgical limb were obtained before (Pre) and after training. Molecular end points and muscle function data were also compared with matched nonexercise healthy controls (CON). As a follow-up analysis, we evaluated specific sphingolipid pools in HipFx and CON muscle. Following training, quadriceps cross-sectional area, strength, and 6-min walk (6MW) increased in the surgical limb (P < 0.05). Additionally, MYD88, TAK1, NFKB1, IL6, SPT2, and CERS1 gene expression decreased after training (P ≤ 0.05), but some remained elevated above CON levels. Interestingly, MYD88 mRNA was inversely correlated to quadriceps CSA, strength, and 6MW. Finally, muscle dihydroceramides and phosphoceramides in HipFx were lower than CON at Pre (P ≤ 0.05), but after training differences from CON were removed. Together, our pilot data support that exercise training alters skeletal muscle inflammation and ceramide metabolism associated with TLR signaling in older adults recovering from hip fracture surgery and may be related to improvements in muscle function recovery.
  
  
  
  These pilot data demonstrate that 3 mo of exercise training in older adults recovering from hip fracture surgery was able to mitigate skeletal muscle gene expression related to inflammation and ceramide metabolism while also improving surgical limb lean tissue, strength, and physical function.
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
authors: Alec I
authors: AI
authors: McKenzie
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
authors: Robert A
authors: RA
authors: Briggs
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
authors: Katherine M
authors: KM
authors: Barrows
authors: Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.
authors: Daniel S
authors: DS
authors: Nelson
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
authors: Oh Sung
authors: OS
authors: Kwon
authors: Division of Cardiovascular Medicine, University of Utah, Salt Lake City, Utah; and.
authors: Paul N
authors: PN
authors: Hopkins
authors: Department of Orthopaedics, University of Utah, Salt Lake City, Utah.
authors: Thomas F
authors: TF
authors: Higgins
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
authors: Robin L
authors: RL
authors: Marcus
authors: Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah; micah.drummond@hsc.utah.edu.|Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.|Division of Diabetes, Metabolism and Endocrinology, University of Utah, Salt Lake City, Utah.
authors: Micah J
authors: MJ
authors: Drummond
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000368:Aged; D002518:Ceramides / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005121:Extremities / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006620:Hip Fractures / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D053580:Muscle Strength / Q000235:genetics; D010865:Pilot Projects; D052097:Quadriceps Muscle / Q000378:metabolism*; D055070:Resistance Training / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*; D016138:Walking / Q000502:physiology
chemical_list: D002518:Ceramides; D051193:Toll-Like Receptors; C109343:dihydroceramide
keywords: TLR4; atrophy; inflammation; resistance exercise; sphingolipids