Biology subjects

Alquier-Bacquie, V.

Publications and source records attributed to Alquier-Bacquie, V..

4 recordsLinked to original sources

bioRxiv2026

Diet modulates metabolic and hepatic responses to chronic pesticide mixture exposure in mice

Chronic exposure to pesticide mixtures through diet is common, yet their combined metabolic effects and interactions with dietary factors remain unclear. We identified four pesticides prevalent in human exposure (imazalil, thiabendazole, boscalid, lambda-cyhalothrin) and assessed their combined impacts on hepatic metabolism and metabolic homeostasis using human liver cells and male mice fed standard chow or western diets. We found that the pesticide mixture induced metabolic perturbations in human hepatocytes. In addition, the pesticide mixture altered hepatic gene expression in chow-fed mice and exacerbated western diet-induced glucose intolerance, fasting hyperglycemia, and insulin resistance without affecting body weight or liver steatosis. These findings reveal that dietary context influences the metabolic consequences of pesticide mixtures, highlighting the need to consider nutritional status when evaluating environmental contaminant risks. Our results suggest that pesticide mixtures at reference doses may contribute to metabolic dysregulation, particularly under obesogenic dietary conditions. Highlights- Four common pesticides in mixture disrupt metabolism in liver cells - Dietary exposure to this pesticide mixture alters hepatic gene expression in mice - The pesticide mixture exacerbates WD-induced disruptions in glucose homeostasis - Pesticides and diet interact in producing the metabolic effects of a pesticide mixture

pharmacology and toxicology↗

bioRxiv2025

Soluble and insoluble dietary fibres differentially affect liver steatosis and gut microbiota in western-diet fed mice

ScopeMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic hepatic liver disease. An imbalance diet, rich in lipids and sugars and low in fibre, is a key contributing factor. However, there is limited knowledge about how soluble and fermentable dietary fibres, compared to insoluble and non-fermentable fibres, differently affect liver metabolism through their interactions with the intestinal microbiota. Methods and resultsMale mice housed at thermoneutrality were fed a Western Diet (WD) supplemented with fermentable inulin or non-fermentable cellulose for 18 weeks. Inulin supplementation mitigated WD-induced obesity, glucose intolerance, dyslipidemia and protected against WD-induced hepatic steatosis compared to cellulose. Hepatic gene expression changes induced by WD were attenuated with inulin. Additionally, inulin preserved gut microbiota composition and metabolism, indicating greater resilience against diet-induced perturbations. ConclusionThese findings suggest that soluble dietary fibres like inulin confer superior metabolic and hepatic benefits over insoluble fibres by modulating the gut microbiota-liver axis, highlighting their potential role in MASLD management.

physiology↗

bioRxiv2025

Hepatocyte FGF21 is not required for fasting-induced metabolic responses but guides protein appetite after energy depletion

Fasting initiates a coordinated metabolic response to preserve energy balance. As glycogen stores are depleted, the body transitions to mobilizing fatty acids from adipose tissue and generating ketone bodies in the liver to sustain the function of vital organs. A network of hormonal signals and transcriptional programs coordinate these adaptations. Among these, the hepatokine fibroblast growth factor 21 (FGF21) is strongly upregulated during fasting and has been proposed as a key mediator of the fasting response. To investigate the physiological functions of FGF21, we studied mice with hepatocyte-specific deletion of Fgf21. Although the liver is the primary source of circulating FGF21 during fasting, its absence in hepatocytes did not alter typical fasting-induced gene expression or key metabolic pathways such as hepatic gluconeogenesis, adipose tissue lipolysis, or ketone production. Instead, we uncovered a distinct role for FGF21 in promoting protein appetite following a fast. These findings challenge the conventional view of hepatocyte-produced FGF21 as a fasting-acting hormone and reveal a more specialized function in guiding nutrient selection after energy depletion.

physiology↗

bioRxiv2024

Effect of thermoneutral housing on MASLD severity, hepatic gene expression, and BAT activation during beta3-adrenergic stimulation in mice

Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. No medication is approved for MASLD treatment, and relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis, and evaluate therapeutic approaches. Here we demonstrated that compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, compared to standard-housed mice, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis. The liver is the central metabolic organ in whole-body metabolic homeostasis. We used thermoneutrally housed mice with WD-induced MASLD to examine the effect of MASLD during {beta}3- adrenergic stimulation, and found that diet-induced MASLD was associated with defective inter- organ metabolic cross-talk, leading to impaired brown adipose tissue activation. HighlightsO_LIThermoneutral housing promotes WD-induced obesity and MASLD in mice C_LIO_LIThermoneutral housing fosters WD-induced change in gene expression C_LIO_LIThermoneutral housing fosters hepatic inflammation and fibrosis C_LIO_LIMASLD is associated with defective BAT response to {beta}3-adrenergic stimulation C_LI

physiology↗