Upregulation of Tribbles decreases body weight and increases sleep duration.
Rebeka PopovicYizhou YuNuno Santos LealGiorgio FedeleSamantha H Y LohLuis Miguel MartinsPublished in: Disease models & mechanisms (2023)
Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases act as negative regulators of insulin signalling. Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. Type 2 diabetes mellitus is associated with increased body weight, sleep problems and increased long-term mortality. Here, we investigated how manipulating the expression of Tribbles impacts body weight, sleep and mortality. We showed that the overexpression of Drosophila tribbles (trbl) in the fly fat body reduces both body weight and lifespan in adult flies without affecting food intake. Furthermore, it decreases the levels of Drosophila insulin-like peptide 2 (DILP2; ILP2) and increases night-time sleep. The three genes encoding TRIBs of mammals, TRIB1, TRIB2 and TRIB3, show both common and unique features. As the three human TRIB genes share features with Drosophila trbl, we further explored the links between TRIB genetic variants and both body weight and sleep in the human population. We identified associations between the polymorphisms and expression levels of the pseudokinases and markers of body weight and sleep duration. We conclude that Tribbles pseudokinases are involved in the control of body weight, lifespan and sleep.
Keyphrases
- body weight
- sleep quality
- drosophila melanogaster
- poor prognosis
- physical activity
- type diabetes
- endothelial cells
- glycemic control
- insulin resistance
- genome wide
- cell proliferation
- adipose tissue
- cardiovascular events
- cardiovascular disease
- risk factors
- dna methylation
- mental health
- genome wide identification
- polycystic ovary syndrome
- long non coding rna
- skeletal muscle
- pluripotent stem cells
- single molecule
- cardiovascular risk factors
- reactive oxygen species
- mass spectrometry