Philippe, M. A. | bioRxiv Science

bioRxiv2025

BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity

Contemporary lifestyle modifications such as changes in nutritional and sleep/wake rhythms increase the risk of metabolic and inflammatory complications linked to obesity, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). BMAL2 (Brain and Muscle ARNT Like Protein 2) is a transcription factor belonging to the circadian clock transcriptional feedback loop which synchronizes internal biological rhythms to environment. In humans, reduced expression in white adipose tissue (WAT) and specific polymorphisms of BMAL2 are associated with obesity and T2D. In this study we report that Bmal2 invalidation in mice leads to increased body weight gain during diet-induced obesity. Loss of BMAL2 triggers the inflammatory response by increasing Tnf expression and modifying adipocyte progenitor fate. This results in reduced lipid storage capacity within the WAT and increased ectopic storage in the liver. These functional and structural alterations culminate in the onset of hepatic steatosis and insulin resistance in liver and WAT. Overall, our investigations underscore the role of BMAL2 in the development and function of adipocytes, as well as in their inflammatory potential within the WAT. Our findings contribute to the understanding of the role of circadian clock genes in obesity and interconnected metabolic complications. HighlightsO_LIThe transcription factor BMAL2 is involved in metabolic complications of obesity in a mouse model of diet-induced obesity C_LIO_LIInvalidation of Bmal2 worsens insulin resistance and hepatic steatosis induced by high fat diet C_LIO_LIInvalidation of Bmal2 impairs visceral adipose tissue adaptation capacity in promoting inflammation and adipose progenitor decline C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/641984v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1d60e1eorg.highwire.dtl.DTLVardef@38daaaorg.highwire.dtl.DTLVardef@9c0040org.highwire.dtl.DTLVardef@1d484bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2023

Association between the magnitude of melatonin circadian rhythm and personality in the threespine stickleback.

Melatonin secretion follows a circadian pattern with a maximum level at night in many species. However, in zebrafish (Danio rerio, a diurnal fish species) large inter-individual variations in daily rhythmicity of melatonin levels are present and are associated with variation in behaviour. Melatonin secretion rhythm of proactive individuals that are more active and exploratory are of larger amplitude compared to reactive individuals. In threespine sticklebacks (Gasterosteus aculeatus), a nocturnal species, inter-individual variability of behaviour is well described. However, inter-individual variation of melatonin rhythm and its association with variation in behaviour has never been measured in this species, which would allow to test if patterns found in zebrafish can be generalized for diurnal and nocturnal species. We measured large inter-individual variation in melatonin levels and found that activity was positively correlated with plasma melatonin concentration measured at night. We did not observe any significant difference in nigh-day variation in melatonin concentration between very active and less active groups. However, we found that individuals classified as reactive based on their propensity to wall-hugging, a measure of anxiety in fish, showed large variation in melatonin between night and day, while this rhythm was not seen in proactive individuals that frequently used the centre of the aquarium. Overall, our study suggests that melatonin may directly modulate specific behaviours in wild sticklebacks, and that while interindividual variation in melatonin rhythm may be widespread in fish, different patterns of association with behaviours should be expected.

physiology↗