Michael N, Gupta V, Sadananthan SA, Sampathkumar A, Chen L, Pan H, Tint MT, Lee KJ, Loy SL, Aris IM, Shek LP, Yap FKP, Godfrey KM, Leow MK, Lee YS, Kramer MS, Henry CJ, Fortier MV, Seng Chong Y, Gluckman PD, Karnani N, Velan SS. “Determinants of intramyocellular lipid accumulation in early childhood”. Int J Obes (Lond). 2019 Aug 28. doi: 10.1038/s41366-019-0435-8.
Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood.
This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6.
The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6.
This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.
This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding was provided by the Strategic Positioning Fund (SPF) and the Joint Council Office (JCO, 1431AFG110, available to NK) from Agency for Science Technology and Research (A*STAR), Singapore. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (as an NIHR Senior Investigator (NF-SI-0515-10042) and through the NIHR Southampton Biomedical Research Centre) and the European Union’s Seventh Framework Programme (FP7/2007-2013), projects Early Nutrition and ODIN under grant agreement numbers 289346 and 613977.