Translocation of gut microbes to epididymal white adipose tissue drives lipid metabolism disorder under heat stress

Deng, Zhang-Chao; Yang, Jiacheng; Huang, Yuxuan; Zhao, Ling; Zheng, Jinshui; Xu, Qingbiao; Guan, Leluo; Sun, Luo

doi:10.1007/s11427-022-2320-y

Cited by 15 publications

(2 citation statements)

References 86 publications

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“…could treat HS‐induced lipid metabolism disorders. 94 Ruminococcus spp. is closely associated with inflammatory bowel disease and neurological disorders.…”

Section: Discussionmentioning

confidence: 99%

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BHBA attenuates endoplasmic reticulum stress‐dependent neuroinflammation via the gut–brain axis in a mouse model of heat stress

Sui,

Feng,

et al. 2024

CNS Neurosci Ther

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BackgroundHeat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β‐Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti‐inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms.MethodsAn in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS‐induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH‐DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents.ResultsHeat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF‐α, IL‐1β, and IL‐6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti‐inflammatory cytokines (IL‐10), while also inhibiting HS‐induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF‐α and IL‐1β) in mouse BV2 cells.Conclusionβ‐Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut–brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

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“…could treat HS‐induced lipid metabolism disorders. 94 Ruminococcus spp. is closely associated with inflammatory bowel disease and neurological disorders.…”

Section: Discussionmentioning

confidence: 99%

“…found that Lactobacillus spp. could treat HS‐induced lipid metabolism disorders 94 . Ruminococcus spp.…”

Section: Discussionmentioning

confidence: 99%

BHBA attenuates endoplasmic reticulum stress‐dependent neuroinflammation via the gut–brain axis in a mouse model of heat stress

Sui,

Feng,

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken

Deng,

Yang,

Feng

et al. 2024

Sci. China Life Sci.

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Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice

Wang,

Gong,

Fang

et al. 2024

Sci. China Life Sci.

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Translocation of gut microbes to epididymal white adipose tissue drives lipid metabolism disorder under heat stress

Cited by 15 publications

References 86 publications

BHBA attenuates endoplasmic reticulum stress‐dependent neuroinflammation via the gut–brain axis in a mouse model of heat stress

BHBA attenuates endoplasmic reticulum stress‐dependent neuroinflammation via the gut–brain axis in a mouse model of heat stress

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken

Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice

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