Determinants of intramyocellular lipid accumulation in early childhood

Abstract

Background/Objectives 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. Subjects/Methods 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. Results 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. Conclusion 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.

Brown Adipose Tissue, Adiposity, and Metabolic Profile in Preschool Children

“…The underlying mechanism for this observation is not known. However, our findings of ethnic differences in adiposity and IMCL is consistent with previous findings in the GUSTO cohort ( 21 , 27 ). We have previously shown interethnic variations in insulin sensitivity.…”

The Role of Vegan Diets in Lipotoxicity-Induced Beta-Cell Dysfunction in Type-2-Diabetes

“…71 The latter refers to the ectopic deposition of FFA in muscle cells, which ultimately results in insulin resistance. [72][73][74] A low-fat vegan diet has been frequently suggested to reduce intramyocellular lipid accumulation, 70,75 indirectly indicating that lipotoxic effects can be modified with dietary modification.…”

The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate With Early Childhood Adiposity

“…This is suggestive of greater inflammatory activation of the catalytic steps mediated by IDO in Indian neonates. The biological significance of this sexual dimorphism and these ethnic variations are unknown; however, the GUSTO study has established the presence of heightened adiposity and early onset of increased metabolic risk in childhood for those of Indian ethnicity relative to Chinese and Malay children ( 30 , 31 , 34 ).…”