Abstract
BackgroundObese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). However, the exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be specifically induced. In the current study, we aimed to establish a protocol for the use of zebrafish as a model for obesity-related metabolically healthy versus metabolically unhealthy AT accumulation.MethodsWe overfed adult male zebrafish of the AB strain with normal fat diet (NFD) or high fat diet (HFD) for 8 weeks and compared parameters related to obesity, i.e. body weight, body mass index, condition index and body fat percentage, to control zebrafish fed under physiological conditions. In addition, we investigated the presence of early obesity-related metabolic alterations by quantifying blood glucose levels, plasma triglyceride and cholesterol levels, and by assessing ectopic lipid accumulation in the liver of zebrafish. Finally, we determined gene expression levels of marker genes related to lipid metabolism, inflammation and fibrosis in visceral AT and liver.ResultsWe show that 8-weeks overfeeding with either NFD or HFD leads to a significant increase in body weight and AT mass compared to controls. In contrast to NFD-overfed zebrafish, HFD-overfed zebrafish additionally present metabolic alterations, e.g. hyperglycemia and ectopic lipid accumulation in the liver, and a metabolically unhealthy AT phenotype with adipocyte hypertrophy especially in the visceral AT depot, which is accompanied by changes in the expression of marker genes for lipid metabolism, inflammation and fibrosis.ConclusionsIn summary, we have established a method for the specific induction of metabolically distinct obesity phenotypes in zebrafish. Our results indicate that zebrafish represents an attractive model to study regulatory mechanisms involved in the determination of AT phenotype during development of metabolically healthy versus metabolically unhealthy obesity.
Highlights
Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution and adipose tissue (AT) phenotype
Depending on body fat distribution and AT phenotype obese individuals differ in their susceptibility to obesity-associated diseases, such as hepatic steatosis and type 2 diabetes [4,5,6]
The identification of mechanisms involved in the determination of body fat distribution and/or AT phenotype during obesity development are limited by the lack of suitable in vivo models, in which metabolically healthy versus metabolically unhealthy AT accumulation can be induced
Summary
Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). The exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be induced. Depending on body fat distribution and AT phenotype obese individuals differ in their susceptibility to obesity-associated diseases, such as hepatic steatosis and type 2 diabetes [4,5,6]. The identification of mechanisms involved in the determination of body fat distribution and/or AT phenotype during obesity development are limited by the lack of suitable in vivo models, in which metabolically healthy versus metabolically unhealthy AT accumulation can be induced. The zebrafish has become increasingly important for the identification of genes or potential drugs regulating lipid metabolism, AT accumulation and associated processes [9, 16]
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