Clock Modulation by Naringenin via RORα Suppresses Lipogenesis and Promotes Adipose Tissue Browning.

No SJR dataSep 15, 2025bioRxiv : the preprint server for biology

Naringenin may control body clock to reduce fat creation and increase fat burning in fat tissue

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Naringenin administration in vivo resulted in reduced fat mass and body weight.

Naringenin activates a specific protein (RORα) that influences circadian rhythms in fat cells.
This compound suppresses lipid storage in fat cells and encourages the development of brown fat, which burns energy.
The beneficial effects of naringenin on fat storage are linked to its impact on circadian clock regulation, as these effects were not observed in fat cells lacking RORα.
In vivo treatment with naringenin increased RORα levels and enhanced the expression of clock-related genes, contributing to improved metabolic functions.
Naringenin administration lowered plasma glucose and free fatty acid levels while improving insulin signaling in both fat and muscle tissues.

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The circadian clock orchestrates adipocyte development and lipid remodeling, with its disruption leading to the development of obesity and insulin resistance. Here we demonstrate that the flavonoid compound naringenin displays clock modulatory activity via RORα that suppresses adipocyte lipid storage while promoting browning. In adipogenic progenitors, naringenin activates RORα with induction of clock gene expression to promote circadian clock oscillation with protective effect against cytokine-induced dampening. The clock-enhancing properties of naringenin suppressed lipogenesis in mature adipocytes together with induction of browning characteristics. The inhibitory effect of naringenin on lipogenesis was dependent on clock modulation as it was abolished in RORα-deficient adipocytes. We further show that naringenin administration in vivo up-regulated RORα expression with clock gene induction together with browning of subcutaneous beige fat depot, resulting reduced fat mass and body weight. Naringenin treatment in vivo also lowered plasma glucose and free fatty acid levels, with markedly enhanced insulin signaling in adipose depots and skeletal muscle. Collectively, our findings uncover a new clock-activating mechanism of action in mediating the metabolic benefits of naringenin, suggesting its potential as a natural supplement for anti-obesity and metabolic disease interventions.