Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth

Abstract

Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB/N and obesity-prone C57BL/6, were measured after 2, 4, and 12 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover.

Adipose cell hypertrophy precedes the appearance of small adipocytes by 3 days in C57BL/6 mouse upon changing to a high fat diet

“…8 Mathematical modeling has proven powerful to quantitatively resolve adipose tissue dynamic at the cellular level, illustrating expansion of adipose tissue and precursor recruitment. [9][10][11] Here, we investigate in a mouse model if there is a specific delay between an increase in caloric intake and the recruitment of new adipocytes, and if there are other dynamic changes in adipose tissue lipolysis and lipid uptake concomitant with such an increase.…”

Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

“…Those models invoke a growth law in which growth accelerates as cell size increases and eventually declines at very large size. 34,35 This will generally produce a pronounced left tail and a nadir to the left of the right peak. Note that, while not unimodal, the distribution is not a standard bimodal distribution (sum of two Gaussian curves).…”

Macro fat and micro fat: insulin sensitivity and gender dependent response of adipose tissue to isocaloric diet change

“…9 Moreover, obese individuals have distinct cell-size distribution patterns compared with normal weight individuals in both human and animal studies. 8,10 Therefore, the adipose cell-size distribution may be an important factor associated with the etiology of obesity and type 2 diabetes. 8,11 Adipose cell number and size are not static.…”

“…new cell recruitment, cell growth/shrinkage, lipid turnover, and cell death) can lead to changes in adipose cell-size distributions over the life of an individual. 10,12,13 Correspondingly, a change in fat mass is associated with a change in the adipose cellsize distribution, which includes information on cell sizes and numbers. Quantitative elucidation of the relationship of whole body fat mass changes, the macroscopic level, and adipose cellsize and number changes, the microscopic level, in response to physiological stimuli and energy intake is essential to understand the development of obesity, as adipose tissue state is historydependent.…”

“…Quantitative elucidation of the relationship of whole body fat mass changes, the macroscopic level, and adipose cellsize and number changes, the microscopic level, in response to physiological stimuli and energy intake is essential to understand the development of obesity, as adipose tissue state is historydependent. 9,10,12,13 However, little is known about the relationship between metabolic state, changes in macroscopic fat mass, and associated changes in microscopic adipose tissue morphology.…”