Adipose cell and lipid turnovers in obesity and insulin resistance

Excerpt

The correlation between the twin epidemics of obesity and insulin resistance is well established on a population level. However, the association between the degree of obesity and the development of insulin resistance is less obvious at the individual level, although there should be a mechanistic link that specifically and differentially connects the two conditions. To identify such a link, we must first understand the process of change in vivo in adipocyte number and volume and the regulation of lipid storage and removal in both lean and obese individuals. Obesity, characterized by expanded fat mass, may involve both an increased volume of preexisting adipocytes (hypertrophy) and the generation of new adipocytes (hyperplasia). Whereas methods for measuring the size of fat cells are available, it is more difficult to determine their total number, which can be estimated by dividing total body fat weight by mean adipose cell weight calculated from mean cell diameter [1]. However, the dynamics of fat cell turnover in vivo have not been sufficiently studied. Spalding, Arner, and collaborators [2] investigated these dynamics in humans by measuring the incorporation of atmospheric carbon 14 (¹⁴C) into genomic DNA. They took advantage of the fact that ¹⁴C levels in the atmosphere transiently increased during above-ground nuclear bomb tests between 1955 and 1963 and exponentially decreased after cessation of the tests. ¹⁴C in the atmosphere oxidizes to form carbon dioxide (CO₂), which is taken up into organic components during plant photosynthesis. Because humans eat plants, or animals that live off plants, the ¹⁴C content in the human body parallels that in the atmosphere and can be used to calculate the turnover rate of adipocytes. The study authors first confirmed that adipocyte number in individuals with early onset of obesity is higher than in lean individuals. They then demonstrated that 8.4 % of fat cells are renewed annually at all adult ages and levels of body mass index (BMI). Nevertheless, the adipocyte number stays remarkably constant in adulthood in both lean and obese individuals, which indicates that there should be a mechanism to closely balance their birth and death rates, even in the obese, and that the difference in adipocyte number between lean and obese individuals is established during childhood. In support of this, Spalding et al. found no significant difference in the average age of adipocytes in lean versus obese individuals. Therefore, hyperplastic obesity, which is most marked in early-onset, severely obese individuals [3, 4], is determined by genetic factors or by nutrient states in childhood. These findings also suggest that weight change in adulthood is primarily the result of changes in adipocyte volume. It was reported that in a population-based sample, adipocyte hypertrophy is associated with decreased insulin sensitivity, even in lean and apparently healthy individuals [5]. This may be relevant to the hypothesis that larger adipocytes secrete proportionally more proinflammatory adipocytokines than anti-inflammatory adipocytokines compared with smaller adipocytes, as was previously reported [6]. …