Forsøksdyr: Regulation of body mass/adipocyte differentiation by Sumo

Godkjenningsdato 10.12.2018

Godkjenningsperiode 01.03.2019-28.02.2023

I. We have preliminary data suggesting that the small ubiquitin-like modifier Sumo is involved in adipose tissue homeostasis ex vivo. Although we can’t disclose any details at the moment, we now need to bring our project to the next level by performing experiments in vivo. The goal of these experiments is to investigate the role of Sumo in adipose tissue homeostasis in mice.

II. In these experiments we will feed mice on normo diet (ND) or High-fat diet (HFD, ~60% fat). Although feeding mice on HFD triggers obesity and steatosis, it is not a terminal condition, and does nor trigger significant adverse effects on the animal. Furthermore, this condition is reversible by switching animals back to ND.

III. Obesity and associated co-morbidities is reaching pandemic proportions in Western society. This triggers increasing health care burden and decreases life expectancy. This has rendered indispensable the study of adipocyte differentiation and biology using multidisciplinary approaches. Thanks to these experiments we will uncover a new layer of regulation of body weight. These data will therefore help understanding the genetics/biochemistry features of obese patients that are resistant to medical diet.

IV. In total we will house about 150 mice in the facility with the purpose of performing experiments and maintaining the line.

V. Requirements for 3R

Replacement: The goal of this experiment is to analyze the impact of a mutation on body weight and liver metabolism. This experiment is based on preliminary data obtain in cell lines, but we must now validate our results in the context of a whole animal. Indeed, body weight and liver metabolism can only be studied in vivo.

List the databases and search terms you have used, searching for alternatives: PubMed: 3T3-L1, human adipose stem cells, mice, obesity, sumo, high fat diet, body weigh, glucose, insulin, steatosis, white adipose tissue, brown adipose tissue

Reduction: We will use 40 mice per condition, which will suffice to reach statistical relevance. Plus, our treatment is reversible, so if after 80 weeks (or before) mutant mice fed on HFD do not show any difference when compared to wild-type mice fed on HFD, we will switch both groups back to ND and they will lose weight until they become normal again.