Cover Story Current Issue

Weaning involves a dietary switch in mammals, progressively decreasing the reliance on the consumption of a fat-rich milk diet in favour of a carbohydrate-rich diet. Metabolic adaptation to this shift in macronutrient consumption is characterized by reduced hepatic gluconeogenesis, increased liver glycogen content, and changes in lipid metabolism. Such metabolic changes are supported by various nutritional, hormonal, and neuronal factors. Dietary changes during weaning are shown to drive β-cell proliferation and maturation, which is important for the optimal endocrine function of the pancreas. A switch from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5′-adenosine monophosphate-activated protein kinase (AMPK) was found critical for functional maturation of β-cells. Furthermore, changes in the macronutrient composition during the weaning process drive alterations in the gut microbiome, which is essential for the development of immune tolerance. The major calcium absorption pathway also changes during weaning, from the paracellular pathway during the suckling stage to the vitamin D dependent transcellular pathway post-weaning. However, the factors that regulate these post-weaning metabolic adaptations are not fully understood.

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Current Issue

IL-6 decodes sex and diet-dependent circadian and metabolic rhythms

Antía González-Vila, Ali Mohammad Ibrahim-Alasoufi, María Luengo-Mateos, Víctor Pardo-García, ... Olga Barca-Mayo

IL-6 decodes sex and diet-dependent circadian and metabolic rhythms

 

Objective

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation and energy metabolism. Its diurnal secretion influences core circadian components, emphasizing its critical role in circadian biology. Despite known sex differences in immune, circadian, and metabolic processes, how IL-6 integrates these processes remains poorly understood.

Methods

IL6 knockout (KO) and control mice of both sexes were phenotyped for circadian and metabolic traits under standard (STD) and high-fat diet (HFD), fasting, and time-restricted feeding. Molecular analyses in muscle, liver, and hypothalamus assessed clock gene expression and IL-6 signaling pathway. Circulating sex steroid hormones were quantified to examine their contribution to the observed sex-specific phenotypes.

Results

IL-6 deficiency disrupts circadian locomotor and metabolic rhythms in a sex- and diet-dependent manner. Males exhibit impaired light-driven circadian rhythms under STD conditions and metabolic misalignment under HFD, whereas females display greater circadian resilience under STD conditions but increased vulnerability to circadian disruption during HFD. Additionally, IL-6 emerges as a novel regulator of the food-entrainable oscillator (FEO), linking food anticipatory activity and metabolic cycles under both STD and HFD in a sex-dependent manner.

Conclusions

These findings identify IL-6 as a critical mediator of circadian-metabolic plasticity, shaping sex- and diet-specific trade-offs between circadian stability and metabolic homeostasis. Our study highlights IL-6 as a potential therapeutic target for mitigating circadian misalignment-associated metabolic disorders, with implications for the timed modulation of IL-6 signaling.

 

 

Articles in Press

IL-6 decodes sex and diet-dependent circadian and metabolic rhythms

Antía González-Vila, Ali Mohammad Ibrahim-Alasoufi, María Luengo-Mateos, Víctor Pardo-García, ... Olga Barca-Mayo

IL-6 decodes sex and diet-dependent circadian and metabolic rhythms

 

Objective

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation and energy metabolism. Its diurnal secretion influences core circadian components, emphasizing its critical role in circadian biology. Despite known sex differences in immune, circadian, and metabolic processes, how IL-6 integrates these processes remains poorly understood.

Methods

IL6 knockout (KO) and control mice of both sexes were phenotyped for circadian and metabolic traits under standard (STD) and high-fat diet (HFD), fasting, and time-restricted feeding. Molecular analyses in muscle, liver, and hypothalamus assessed clock gene expression and IL-6 signaling pathway. Circulating sex steroid hormones were quantified to examine their contribution to the observed sex-specific phenotypes.

Results

IL-6 deficiency disrupts circadian locomotor and metabolic rhythms in a sex- and diet-dependent manner. Males exhibit impaired light-driven circadian rhythms under STD conditions and metabolic misalignment under HFD, whereas females display greater circadian resilience under STD conditions but increased vulnerability to circadian disruption during HFD. Additionally, IL-6 emerges as a novel regulator of the food-entrainable oscillator (FEO), linking food anticipatory activity and metabolic cycles under both STD and HFD in a sex-dependent manner.

Conclusions

These findings identify IL-6 as a critical mediator of circadian-metabolic plasticity, shaping sex- and diet-specific trade-offs between circadian stability and metabolic homeostasis. Our study highlights IL-6 as a potential therapeutic target for mitigating circadian misalignment-associated metabolic disorders, with implications for the timed modulation of IL-6 signaling.

 

 

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Diabetes Conference 
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2022 impact factor: 6.6

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