Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

Abstract

OBJECTIVEAdipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology.RESEARCH DESIGN AND METHODSSubcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18–60 kg/m2. A morphology value was defined as the difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric 14C into DNA.RESULTSOccurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (β-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = −0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (∼10% per year) or mean age of adipocytes (∼10 years) was not correlated with morphology.CONCLUSIONSAdipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia.

Semaphorin 3C is a novel adipokine linked to extracellular matrix composition

“…In our experimental set-up, neither the expression nor secretion of SEMA3C by cultured human adipocytes was affected by reduced oxygen tension, suggesting that SEMA3C production by fat cells is regulated via hypoxia-independent mechanisms which need to be further investigated. The observation that SEMA3C expression correlated significantly with adipocyte morphology (a measure that is independent of body fat mass as discussed [18]) demonstrates that there is a link between relative fat-cell size and SEMA3C levels. Fat-cell morphology is determined by adipocyte [18] and lipid turnover [44].…”

“…The observation that SEMA3C expression correlated significantly with adipocyte morphology (a measure that is independent of body fat mass as discussed [18]) demonstrates that there is a link between relative fat-cell size and SEMA3C levels. Fat-cell morphology is determined by adipocyte [18] and lipid turnover [44]. However, the transcriptional networks that regulate these processes have not yet been determined and their potential role in regulating SEMA3C requires further investigation.…”

“…previously not characterised in human WAT/adipocytes). We found that SEMA3C was predominantly expressed in fat cells and that its expression and secretion correlated with hypertrophic WAT (fewer but larger fat cells, a phenotype associated with in vivo insulin resistance [18,35]) and independent measures of in vivo whole-body insulin resistance (HOMA IR , K ITT ), regardless of BMI. Recombinant SEMA3C did not have any direct metabolic effects on human adipocytes in culture.…”

“…Adipocyte morphology (i.e. the relative fat-cell size in relation to total fat mass) has been shown to correlate with insulin sensitivity and was determined as described [18].…”

The contribution of bone marrow-derived cells to the human adipocyte pool

“…Thus, irrespective of body fat mass, subjects with adipose hypertrophy (few but large fat cells), display significantly reduced adipocyte turnover rates compared with age and body weight matched subjects with hyperplasia (many small fat cells). 3 Furthermore, adipose hypertrophy associates with insulin resistance/type 2 diabetes while hyperplasia is protective. [4][5][6] This suggests that influencing adipogenesis and thereby adipocyte number could have therapeutic implications in common metabolic disorders, a hypothesis supported by the antidiabetic actions of thiazolidinediones.…”