Early life nutrition modulates muscle stem cell number: implications for muscle mass and repair.
Suboptimal nutrition during prenatal and early postnatal development is associated with increased risk for type 2 diabetes during adult life. A hallmark of such diabetes risk is altered body composition, including reduced lean mass and increased adiposity. Since stem cell number and activity are important determinants of muscle mass, modulation of perinatal nutrition could alter stem cell number/function, potentially mediating developmentally programmed reductions in muscle mass. Skeletal muscle precursors (SMP) were purified from muscle of mice subjected to prenatal undernutrition and/or early postnatal high-fat diet (HFD)--experimental models that are both associated with obesity and diabetes risk. SMP number was determined by flow cytometry, proliferative capacity measured in vitro, and regenerative capacity of these cells determined in vivo after muscle freeze injury. Prenatally undernutrition (UN) mice showed significantly reduced SMP frequencies [Control (C) 4.8% ± 0.3% (% live cells) vs. UN 3.2% ± 0.4%, P=0.015] at 6 weeks; proliferative capacity was unaltered. Reduced SMP in UN was associated with 32% decrease in regeneration after injury (C 16% ± 3% of injured area vs. UN 11% ± 2%; P<0.0001). SMP frequency was also reduced in HFD-fed mice (chow 6.4% ± 0.6% vs. HFD 4.7% ± 0.4%, P=0.03), and associated with 44% decreased regeneration (chow 16% ± 2.7% vs. HFD 9% ± 2.2%; P<0.0001). Prenatal undernutrition was additive with postnatal HFD. Thus, both prenatal undernutrition and postnatal overnutrition reduce myogenic stem cell frequency and function, indicating that developmentally established differences in muscle-resident stem cell populations may provoke reductions in muscle mass and repair and contribute to diabetes risk.
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Melissa
M
Woo
Elvira
E
Isganaitis
Massimiliano
M
Cerletti
Connor
C
Fitzpatrick
Amy J
AJ
Wagers
Jose
J
Jimenez-Chillaron
Mary Elizabeth
ME
Patti
D015502:Absorptiometry, Photon; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D002452:Cell Count; D004041:Dietary Fats / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects; D051379:Mice; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009752:Nutritional Status; D009929:Organ Size; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
D004041:Dietary Fats
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