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

Abstract

Background/objective: Puberty 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/methods: We 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 magnetic resonance imaging, and markers of type 2 diabetes risk were collected at fasting and during an oral glucose tolerance test (OGTT).

Results: Baseline pubertal status significantly moderated the 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±0.08 l vs 0.03±0.10 l; 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, the 2-year increase in HFF and VAT significantly associated with a decline in BCF (ß=-1.04, P=0.038; ß=-1.81, P=0.020) and metabolic function, while accumulation of SAAT significantly associated with BCF (ß=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 (ß=1.00, P=0.034; ß=1.00, P=0.015; ß=01.01, P=0.024).

Conclusions: The 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.

Figure 1. Two-year change in abdominal fat depots by Tanner stage

a. SAAT accumulation does not significantly differ by Tanner stage b. There is a significant difference in VAT change by baseline Tanner stage, with a greater increase in participants with Tanner>3 (p_tanner*time = 0.044) c. There is a significant difference in HFF change by baseline Tanner stage, with a decrease in HFF in participants with Tanner ≤3 and an increase in participants with Tanner>3 (p_tanner*time = 0.007) d. There is a significant difference in PFF change by baseline Tanner stage, with a decrease in PFF in participants with Tanner≤3 and an increase in participants with Tanner>3 (p_tanner*time < 0.001). SAAT= subcutaneous abdominal adipose tissue, VAT= visceral adipose tissue, HFF= hepatic fat fraction, PFF= pancreatic fat fraction

Figure 2. Change in fat depot predicting 2-year change in risk for type 2 diabetes

These lines represent how a 1-SD increase in each fat depot predicts a % change in risk for type 2 diabetes. Relationships that are beneficial to risk for type 2 diabetes have green arrows, while relationships that are detrimental to risk for type 2 diabetes have red arrows. All displayed relationships are significant (p<0.05) and are adjusted for baseline SAAT, VAT, HFF, PFF, tanner, age, sex, total fat and change in total fat, and change in other respective fat depots (SAAT, VAT, HFF, PFF). SAAT= subcutaneous abdominal adipose tissue, VAT= visceral adipose tissue, HFF= hepatic fat fraction, PFF= pancreatic fat fraction, BCF= beta-cell function, IGI= insulinogenic index (insulin secretion), AUC= area under the curve, FFA= free fatty acid