Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

OBJECTIVE

Adipose 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 METHODS

Subcutaneous 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.

RESULTS

Occurrence 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.

CONCLUSIONS

Adipose 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.Adipose tissue expands by increasing the volume of preexisting adipocytes (adipose hypertrophy), by generating new small adipocytes (hyperplasia), or by both. Although the amount and distribution of adipose tissue associate independently with insulin resistance, type 2 diabetes, and other metabolic disorders (1), the size of adipocytes within the adipose tissue is also important (2). Increased adipocyte size correlates with serum insulin concentrations, insulin resistance, and increased risk of developing type 2 diabetes (3–10). Obese subjects with few large adipocytes are more glucose intolerant and hyperinsulinemic than those having the same degree of obesity and many small fat cells (5,7,9–14). Furthermore, adipocyte hypertrophy may impair adipose tissue function by inducing local inflammation, mechanical stress, and altered metabolism (15–17). There is, however, a large interindividual variation in adipocyte size among lean and obese individuals (10,18,19). Lean individuals can have larger adipocytes than obese individuals and the other way around. Hitherto there is no straightforward method to assess adipose morphology. It is not valid to merely adjust fat cell size for BMI by linear regression because the relationship between BMI or fat mass and adipocyte size is curve-linear (10,18,19).The mechanisms responsible for the development of different forms of adipose morphology are unknown; however, adipocyte turnover may be involved. The turnover rate of adipocytes is high at all adult ages and body fat levels (18). Approximately one-tenth of the total fat cell pool is renewed every year by ongoing adipogenesis and adipocyte death.We presently investigated whether adipocyte turnover was involved in the different morphologies of subcutaneous adipose tissue (the body''s dominant fat depot). A method to quantitatively assess adipose morphology was developed. Based on the relationship between adipocyte size and total body fat, the subjects were categorized as having different degrees of either adipose hypertrophy or hyperplasia. Thereafter, we set the different forms of adipose morphology in relation to adipocyte turnover in vivo using previously generated data on the incorporation of atmospheric ¹⁴C into adipocyte DNA (18). Finally, we correlated adipose morphology with fasting plasma insulin and insulin sensitivity in vivo.