Fat Cell Size: Measurement Methods, Pathophysiological Origins, and Relationships with Metabolic Dysregulations

Abstract The obesity pandemic increasingly causes morbidity and mortality from type 2 diabetes, cardiovascular diseases and many other chronic diseases. Fat cell size (FCS) predicts numerous obesity-related complications such as lipid dysmetabolism, ectopic fat accumulation, insulin resistance, and cardiovascular disorders. Nevertheless, the scarcity of systematic literature reviews on this subject is compounded by the use of different methods by which FCS measurements are determined and reported. In this paper, we provide a systematic review of the current literature on the relationship between adipocyte hypertrophy and obesity-related glucose and lipid dysmetabolism, ectopic fat accumulation, and cardiovascular disorders. We also review the numerous mechanistic origins of adipocyte hypertrophy and its relationship with metabolic dysregulation, including changes in adipogenesis, cell senescence, collagen deposition, systemic inflammation, adipokine secretion, and energy balance. To quantify the effect of different FCS measurement methods, we performed statistical analyses across published data while controlling for body mass index, age, and sex.

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Effect of (-)-hydroxycitrate on development of obesity in the Zucker obese rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.240.1.e72 ◽

1981 ◽

Vol 240 (1) ◽

pp. E72-E78 ◽

Cited By ~ 5

Author(s):

M. R. Greenwood ◽

M. P. Cleary ◽

R. Gruen ◽

D. Blase ◽

J. S. Stern ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Cell Size ◽

Treatment Period ◽

Body Fat ◽

Substantial Reduction ◽

Female Rats ◽

Fat Cell ◽

Fat Cell Size ◽

Obese Rats

Young Zucker lean (Fa/-) and obese (fa/fa) female rats were fed the fatty acid synthesis inhibitor (-)-hydroxy-citrate as a dietary admixture for 39 days. In the lean rats, (-)-hydroxycitrate treatment decreased body weight, food intake, percent of body fat, and fat cell size. In the obese rat, food intake and body weight were reduced but the percent of body fat remained unchanged. Throughout the treatment period, obese rats maintained a fat cell size equivalent to their obese controls. Although a reduction in fat cell number in the obese rats occurred during the treatment period, marked hyperplasia was observed during the posttreatment period. The results of this study indicate that the obese rat, despite a substantial reduction in body weight produced by (-)-hydroxycitrate, still defends its obese body composition.

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Effect of weight reduction in the rat on epididymal fat-cell size and relative dispersion

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1974.227.2.420 ◽

1974 ◽

Vol 227 (2) ◽

pp. 420-424 ◽

Cited By ~ 5

Author(s):

JE Smith ◽

M DiGirolamo

Keyword(s):

Cell Size ◽

Weight Reduction ◽

Relative Dispersion ◽

Fat Cell ◽

Fat Cell Size ◽

Epididymal Fat

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Methionine requirement of kittens given amino acid diets containing adequate cystine

British Journal Of Nutrition ◽

10.1079/bjn19830050 ◽

1983 ◽

Vol 49 (3) ◽

pp. 411-417 ◽

Cited By ~ 11

Author(s):

Katherine A. Smalley ◽

Quinton R. Rogers ◽

James G. Morris

Keyword(s):

Adipose Tissue ◽

Cell Size ◽

Muscle Tissue ◽

Dna Content ◽

Shoulder Joint ◽

Subcutaneous Adipose Tissue ◽

Fat Cells ◽

Fat Cell ◽

Fat Cell Size ◽

Subcutaneous Adipose

1. The effects of feeding either high-protein (HP) or low-protein (LP) diets between 1.8 and 15 kg live weight (LW) and a low-energy (LE) or high-energy (HE) intake subsequently on the cellularity of muscle and adipose tissue in pigs growing to 75 kg LW were investigated.2. The effects of the nutritional treatments on muscle tissue were assessed from the weight and DNA content of the m. adductor. For adipose tissue the total DNA content and fat cell size of the subcutaneous adipose tissue contained in the left shoulder joint were determined.3. Feeding the LP diets in early life reduced the weight and DNA content of the m. adductor (P < 0.01) and increased fat cell size (P < 0.01) at 15 kg LW.4. Subsequent to 15 kg there was an almost linear increase in muscle DNA with increasing LW, and the difference between pigs from the initial protein treatments progressively diminished and was no longer apparent at 60 kg LW.5. At 30 kg LW, pigs given the LP diets before 15 kg LW contained less DNA in the subcutaneous adipose tissue from the shoulder joint (P < 0.01) and had larger fat cells (P < 0.05) than pigs given the HP diets initially. However, adipose DNA and fat cell size increased with increasing LW and the differences resulting from the initial protein treatments progressively diminished. On the LE and HE treatments subsequent to 15 kg these differences were no longer evident at 45 and 60 kg respectively.6. Pigs given the HE intake subsequent to 15 kg, contained less DNA in muscle tissue (P < 0·05) at 60 and 75 kg LW and had larger fat cells (P < 0·05) at 45, 60 and 75 kg LW, than pigs on the LE treatment.

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Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms21186836 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6836

Author(s):

Hyo Jin Maeng ◽

Gha Young Lee ◽

Jae Hyun Bae ◽

Soo Lim

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Aortic Arch ◽

Fibroblast Growth Factor ◽

Cell Size ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Plaque Size ◽

Fat Cell ◽

Fat Cell Size

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE−/− mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.

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Development of basal lipolysis and fat cell size in the epididymal fat pad of normal rats

Metabolism ◽

10.1016/0026-0495(80)90066-9 ◽

1980 ◽

Vol 29 (3) ◽

pp. 246-253 ◽

Cited By ~ 16

Author(s):

R. Gruen ◽

R. Kava ◽

M.R.C. Greenwood

Keyword(s):

Cell Size ◽

Fat Pad ◽

Fat Cell ◽

Fat Cell Size ◽

Epididymal Fat

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Influence of feeding level and of protein level in early life on the cellularity of adipose tissue and body fat content of growing pigs

British Journal Of Nutrition ◽

10.1079/bjn19830016 ◽

1983 ◽

Vol 49 (1) ◽

pp. 109-118 ◽

Cited By ~ 3

Author(s):

R. G. Campbell ◽

A. C. Dunkin

Keyword(s):

Adipose Tissue ◽

Cell Size ◽

Body Fat ◽

Subcutaneous Adipose Tissue ◽

Fat Content ◽

Fat Cell ◽

Fat Cell Size ◽

Body Fat Content ◽

Dry Diet ◽

Subcutaneous Adipose

1. The effects of level of feeding and level of protein in the early postnatal period on the cellularity of subcutaneous adipose tissue and body fat content of pigs were investigated in two experiments.2. In Expt 1, piglets were given a common liquid diet at energy intakes equivalent to 2·8 or 5·2 times energy for maintenance (M) between 1·8 and 6·5 kg live weight (LW), and a common dry diet at 2·8 or 4·5 M between 6·5 and 20 kg LW. Between 20 and 75 kg LW all pigs were given a second dry diet at 4·0 M.3. In both experiments the effects of nutritional treatments on fat cell number at 20 and 75 kg LW (Expt 1) and at 45 kg LW (Expt 2) were assessed by measuring the DNA content of the subcutaneous adipose tissue contained in the left shoulder joint. Fat cell size was assessed in the same tissue by measuring the diameter of collagenase-released adipocytes.4. In Expt 1, raising the level of feeding between 1·8 and 6·5 kg LW increased body fat content and average fat cell diameter at both 6·5 (P < 0·01) and 20 kg LW (P < 0·05) but had no effect on either measurement at 75 kg LW. Similarly, raising the level of feeding between 6·5 and 20 kg LW increased body fat content and fat cell size at both 20 (P < 0·01) and 75 kg LW (P < 0·05). There was an almost twofold increase in the DNA content of subcutaneous adipose tisuue between 20 and 75 kg LW. However, it was not significantly affected at either weight by level of feeding before or subsequent to 6·5 kg LW.5. In Expt 2, reducing the level of dietary protein between 1·8 and 6·5 kg LW increased body fat content (P < 0·01) and fat cell size (P < 0·01) at the latter weight. Although level of dietary protein to 6·5 kg LW had no effect on body fat content or the weight of subcutaneous adipose tissue in the shoulder joint at 45 kg LW, pigs given the lowest-protein diet contained less DNA (P < 0·05) in the subcutaneous adipose tissue and had larger (P < 0·05) fat cells than those given the highest-protein diet to 6·5 kg LW. Reducing the protein content of the diet fed subsequent to 6·5 kg LW increased the body fat content (P < 0·01) and fat cell size (P < 0·01) at 45 kg LW.

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Relationships among changes of serum leptin concentration, leptin mRNA expression in white adipose tissue (WAT), and WAT fat-cell size in female Japanese black bears (Ursus thibetanus japonicus)

Canadian Journal of Zoology ◽

10.1139/z08-080 ◽

2008 ◽

Vol 86 (9) ◽

pp. 1042-1049 ◽

Cited By ~ 2

Author(s):

S. Nakamura ◽

T. Okano ◽

H. Shibata ◽

M. Saito ◽

T. Komatsu ◽

...

Keyword(s):

Adipose Tissue ◽

Reproductive Success ◽

Cell Size ◽

White Adipose Tissue ◽

Black Bears ◽

Fat Cell ◽

Serum Leptin ◽

Ursus Thibetanus ◽

Fat Cell Size ◽

The Relationship

As a first step to study the relationship between fat accumulation and reproductive success in Japanese black bears ( Ursus thibetanus japonicus Schlegel, 1857) with the focus on leptin, we determined leptin cDNA sequences in the bears. Next, we studied the possibility of white adipose tissue (WAT) as a leptin secretion source by observing the changes of leptin mRNA expression in WAT by semiquantitative real-time reverse transcript – polymerase chain reaction, the index of WAT fat-cell size, and serum leptin concentration in pregnant bears. Then, based on our results, we discussed roles of leptin in those bears. The amino acid sequences of leptin from the bears were highly identical to that of other carnivores. The expression of leptin mRNA in WAT was detected from September to January, with a tendency to increase in late November and January; the relationship between changes in the index of WAT fat-cell size and those in serum leptin concentration was high (r = 0.55, P < 0.01), with an increase in both in mid-November. These results suggested that leptin was mainly secreted from WAT in bears and that serum leptin concentrations might reflect their nutritional condition. Moreover, leptin might serve as an indicator of their fat mass, which would affect their survival during hibernation and their reproductive success.

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