Saturation of subcutaneous adipose tissue expansion and accumulation of ectopic fat associated with metabolic dysfunction during late and post-pubertal growth.

Abstract

Background/ObjectivePuberty is a period defined by large changes in adipose tissue accumulation and distribution, however longitudinal patterns of ectopic fat development have not been shown. We have previously shown significant declines in beta-cell function (BCF) across puberty and hypothesize that accumulation of ectopic fat deposition, particularly hepatic fat, will predict this fall.Subject/MethodsWe conducted a longitudinal study and examined 2-year change in abdominal fat distribution and type 2 diabetes risk markers in 76 Hispanic children and young adults (16.1 ±0.5 years, 66% obese, 52% male, 51% post-pubertal). Subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT), hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured by 3-Tesla MRI, and markers of type 2 diabetes risk were collected at fasting and during an oral glucose tolerance test (OGTT).ResultsBaseline pubertal status significantly moderated 2-year change in ectopic fat deposition, such that VAT, HFF and PFF increased in individuals during late and post-pubertal growth whereas children earlier in their pubertal development decreased ectopic accumulation and had less VAT accumulation (VAT: pTanner*time =0.044, 0.31±0.08L vs. 0.03±0.10L; HFF: pTanner*time=0.007, 1.34±0.87% vs. −2.61±1.11%; PFF: pTanner*time<0.001, 1.61±0.39% vs. −0.96±0.50%). Independent of pubertal status, two-year increase in HFF and VAT significantly associated with a decline in BCF (β=−1.04, p=0.038; β=−1.81, p=0.020) and metabolic function, while accumulation of SAAT significantly associated with BCF (β=1.36, p=0.012) and metabolic improvement. HFF accumulation was the only depot to significantly predict clinical markers of type 2 diabetes risk, fasting glucose and HbA1c, and circulating free fatty acid levels (β=1.00, p=0.034; β=1.00, p=0.015; β=01.01, p=0.024).ConclusionsThe accumulation of SAAT defends against type 2 diabetes risk and potentially ectopic fat accumulation. Intra-abdominal VAT and HFF accumulation both associate with metabolic decline and BCF, while HFF predicts an even greater number of metabolic risk features.