Using a biologically relevant relationship between the fat mass and adipocyte volume, we developed a novel and apparently valid method to assess quantitatively subcutaneous abdominal adipose tissue morphology. It would also be interesting to study visceral adipose tissue, which is more strongly related to type 2 diabetes and metabolic abnormalities; however, this cannot be investigated in a clinical setting. Whether the inclusion of several rather than only one subcutaneous site would result in an improvement in the accuracy to determine the morphology is not known at present. However, adipocyte sizes in other subcutaneous depots are the strongest determinants of adipocyte size in any given subcutaneous depot (19
). Furthermore, it is not possible for ethical reasons to perform multiple biopsies (abdomen, buttocks, legs, arms, and neck) from lean subjects who were included in this study. There is a large variation in adipocyte size within the same subject and fat depot (25
). Detailed classification requires the separation of isolated adipocytes according to size (15
), which is not feasible using small amounts of adipose tissue.
The occurrence of adipose hypertrophy or hyperplasia was not influenced by sex or body weight (C). This suggests that hyperplasia and hypertrophy are equally common among men and women and evenly distributed among lean, overweight, or obese subjects in a general population. Furthermore, subcutaneous adipose morphology is tightly correlated with the total adipocyte number in the body over a large BMI range (18–60 kg/m2). This may imply that common factors regulate adipose morphology and adipocyte number.
Adipose morphology seems to be related to the generation of new adipocytes. Subjects with hypertrophy generated 70% less adipocytes per year than those with hyperplasia, and there was an inverse quantitative relationship between the residual value for adipocyte volume and adipocyte production rate (i.e., the higher the degree of hypertrophy, the lower the rate of adipocyte formation) (A
). These findings suggest that in hypertrophy, the body produces few adipocytes over time, requiring existing adipocytes to accumulate more lipids in comparison with the hyperplastic state. Age and relative death rate of adipocytes were not influenced by morphology (C
), indicating that the overall percentage of adipocytes replaced each year is similar in hypertrophic and hyperplastic states. Obese individuals have more adipocytes added per year than lean individuals (18
), but the relationship between morphology and adipocyte production is independent of BMI. Thus, de novo adipogenesis is important for both obesity and morphology of human adipose tissue.
Obviously, the volume of adipocytes in adipose tissue is not the same as adipose tissue morphology. Subjects with hypertrophy or hyperplasia can have either small or large adipocytes dependent on their body fat content (A). Thus, absolute adipocyte size is strongly dependent on the degree of overweight/obesity, whereas the difference between observed and expected adipocyte volume, measuring morphology, is adjusted for the fat mass. Furthermore, the nonadjusted adipocyte volume, unlike the morphology value, was not related to adipocyte number (B).
We also found that adipose morphology was an independent regressor for circulating insulin and insulin sensitivity () and that women with hypertrophy had a more adverse metabolic profile and body shape than women with hyperplasia, although BMI was similar in both groups (supplementary Table 1). The true pathophysiological role of adipose morphology must, though, be established by studies of populations selected for risk factor investigation and investigations of visceral adipose tissue.
We investigated a Swedish population. It is not known how the results model other populations. In summary, subcutaneous adipose hypertrophy and hyperplasia occur independently of sex and body fat content and are strongly related to the total adipocyte number in adults. A low generation rate of new adipocytes associates with adipose hypertrophy, which is linked to low insulin sensitivity and high circulating insulin levels. A high rate associates with the more benign adipose hyperplasia.