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Endocrine. 2018 Aug;61(2):317-326. doi: 10.1007/s12020-017-1494-z. Epub 2017 Dec 22.

Metabolic and bone effects of high-fat diet in adult zebrafish.

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Gruppo Ospedaliero San Donato Foundation, Milan, Italy.
Policlinico San Donato IRCCS, Milan, Italy.
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
Diabetes Research Institute, Metabolism, Nutrigenomics and Cellular Differentiation Unit, San Raffaele Scientific Institute, Milan, Italy.
IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.


An increase of visceral fat affects human bone health causing fragility, mechanical strength reduction, and increased propensity to fractures because of impaired bone matrix microstructure and aberrant bone cell function. Adult Danio rerio (zebrafish) represents a powerful model to study both metabolic diseases and bone metabolism. The aim of this study was to generate an obese adult zebrafish by high-fat diet and evaluate metabolic and bone tissue effects. Fish blood glucose and insulin levels were found to be altered in high-fat diet fish revealing a failure in β-cells insulin production. Blood analysis of adipokines revealed significant alterations in adiponectin and leptin levels that are common in human and other obesity animal models. Advanced glycation end products (AGEs), derived from hyperglycemia condition, were found to be altered too. All these alterations were associated with an impaired bone metabolism. The scales of high-fat diet fish shown bone resorption lacunae associated with an intense osteoclastic tartrate-resistant acid phosphatase (TRAP) activity, whereas alkaline phosphatase (ALP) decreased. These data suggest that an imbalance of fat metabolism alters energy metabolism generating an osteoporosis-like phenotype in adult zebrafish scales. The zebrafish obesity model can contribute to elucidate in vivo the molecular mechanisms of metabolic changes in human obese patients.


Bone; Insulin; Obesity; Osteoporosis; Zebrafish

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