Preclinical research in obesity-associated metabolic diseases using in vitro, multicellular, and non-mammalian models

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Addressing the physiological effects of bioactive compounds in metabolic diseases (i.e., obesity, diabetes, liver steatosis) and establishing their mechanisms of action have been a major interest for the last decades. However, methodologies that can be applied to achieve this can vary greatly, leading to a limited type of information. Thus, the accuracy, robustness, reliability and potential (human) translation are highly reliant on the experimental design and selected methodological models. This review presents an update exploring the main features, advantages and disadvantages of most important pre-clinical models used at the present time to study the effects of bioactive compounds on metabolic diseases. Moreover, future challenges in developing new methods are also depicted. In vitro models (enzyme assays and standard two-dimensional cultures of adipocytes, skeletal muscle cells) are intrinsically well established and constitute the first choice and most widely used methods to study bioactive compounds in metabolic diseases. However, novel models such as three-dimensional cultures (spheroids, organoids) are also starting to emerge and complement traditional culture systems. Models of small organisms (C. elegans, D. melanogaster) and non-mammal vertebrates (D. rerio) represent a scientific advantage and a middle-step before traditional mammalian models (rats and mice). This a

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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