Early Life Nutrition Modulates Muscle Stem Cell Number: Implications for Muscle Mass and Repair

Abstract

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 muscleresident stem cell populations may provoke reductions in muscle mass and repair and contribute to diabetes risk.

Impaired Leptin Gene Expression and Release in Cultured Preadipocytes Isolated From Individuals Born With Low Birth Weight

“…In vivo studies of LBW subjects support the idea of fundamental changes in lipid metabolism including increased fasting lipolysis (20) as well as increased nocturnal fat oxidation, potentially associated with an inability to retain fat in the subcutaneous adipose tissue depot (45). A previous study reported reduced numbers of muscle satellite stem cells in mice subjected to prenatal undernutrition (46). Indeed, in vivo fat tissue preadipocyte number could also theoretically be altered and thereby contribute to the increased risk of T2D in LBW subjects (46).…”

The Orphan Nuclear Receptor Nur77 Is a Determinant of Myofiber Size and Muscle Mass in Mice

“…Finally, Nur77's dual role in regulating metabolism and muscle mass raises intriguing questions regarding the interdependence of these two processes. Based on studies examining the impact of nutrition on muscle stem cell function (63,64), we posit that Nur77 coordinates the cross talk between myogenesis and metabolism. Future studies examining the interplay between Nur77, glycolysis, and myogenesis will provide valuable insights into the relationship between metabolism and function, with important implications for conditions such as diabetes and muscle wasting.…”

Skeletal Muscle Stem Cells: Effects of Aging and Metabolism on Muscle Regenerative Function

“…The release of several key growth factors, such as insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), at the site of injury helps to control muscle regeneration by regulating the proliferation and differentiation of satellite cells (Yablonka-Reuveni et al 2008).…”

“…In addition, reflecting the fact that skeletal muscle serves as a major site for glucose storage and insulin uptake, playing a crucial role in overall body metabolism, recent studies indicate that nutrient-dependent changes in satellite cell populations may also modulate stem cell function and homeostasis during aging (Hu et al 2010). For example, diabetic patients can experience delayed healing of injured muscle or limited recovery from skeletal muscle trauma (Gulati and Swamy 1991;Vignaud et al 2007), and recent evidence suggests that excess nutrient intake is associated with defective muscle stem cell function (Woo et al 2011). Conversely, calorie restriction (CR), which extends life span and delays the onset of many age-related diseases in multiple species, appears to preserve stem cell function with age in the hematopoietic system (Ertl et al 2008), and may similarly enhance the regenerative potential of aged satellite cells.…”