Adipocyte Size & Adipokine Secretion

Relationship between Adipocyte Size and Adipokine Expression and Secretion

Context: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to providethe basis for obesity-related complications such as type 2 diabetes and atherosclerosis.

Objective: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion.

Design, Patients, and Main Outcome Measures: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated.

Results: The mean adipocyte volume of the four fractions ranged from 205 ± 146 to 1.077 ± 471 pl. There were stronglinear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-, monocyte chemoattractant protein-1, interferon--inducible protein 10, macrophage inflammatory protein-1ß, granulocyte colony stimulating factor, IL-1ra, and adiponectin was positively correlated with cell size. After correction for cell surface, there was still a significant difference between fraction IV (very large) and fraction I (small cells), for leptin, IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. In contrast, antiinflammatory factors such as IL-1ra and adiponectin lost their association after correction for cell surface area comparing fraction I and IV. In addition, there was a decrease of IL-10 secretion with increasing cell size.

Conclusions: The results clearly suggest that adipocyte size is an important determinant of adipokine secretion. There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.

Fat cells were removed from participants and isolated.  They were then separated into four fractions for each individual.  Fraction I (very small) to Fraction IV (very large).  Plots of the various parameters measured are shown below (see the article for more clarity) comparing the smallest (I) and largest (IV) fractions.

Some excerpts from the discussion:

The results of our study clearly indicate that adipocyte size is an important determinant for the secretion of several adipokines. In particular, the secretion of proinflammatory adipokines is significantly elevated in very large adipocytes compared with small or medium-sized adipocytes, even after correcting for cell volume and surface....

...In contrast to the published studies, which demonstrated associations between average adipocyte size and serum levels or secretion, our study is unique because it investigated the secretory capacity of adipocyte fractions from the same individual separated by cell size. The results obtained by the technique clearly suggest that only the very large adipocytes are dysregulated. Adipocyte hypertrophy appears to cause a differentially impaired secretion between pro- and antiinflammatory adipokines shifting the immunological balance toward the expression of proinflammatory proteins. Thisabnormal function of adipocytes may play an important role in the development of a chronic low-grade proinflammatory state in obesity, which is considered to build the common soil for the development of insulin resistance, type 2 diabetes, and atherosclerosis (5, 68)....

...In conclusion, the results of this study clearly indicate that adipocytes per se are an important production site for manyadipokines, although the relative contribution to the overall secretion from adipose tissue remains to be elucidated.

In the whole chicken-egg debate over obesity and inflammation, it seems that perhaps a certain degree of accumulated fat (large fat cells) sets off the inflammatory environment.   

The discussion in this paper contains quite a lot of background information on both the anti-inflammatory and pro-inflammatory components manufactured in and secreted by adipocytes.  I plan to revisit some of that.

Something else that caught my eye:  Recently, adipocyte size in the sc abdominal depot was identified to be a significant predictor for the future development of diabetes mellitus type 2 (5).  Note:  sc = subcutaneous, not visceral.  Must check this out.