Neural adaption in midbrain GABAergic cells contributes to high-fat diet-induced obesity.

Sci Adv

Department of Neurosurgery of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Key Laboratory for Biomedical Engineering of Education Ministry, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

Published: November 2023

Overeating disorders largely contribute to worldwide incidences of obesity. Available treatments are limited. Here, we discovered that long-term chemogenetic activation of ventrolateral periaqueductal gray (vlPAG) GABAergic cells rescue obesity of high-fat diet-induced obesity (DIO) mice. This was associated with the recovery of enhanced mIPSCs, decreased food intake, increased energy expenditure, and inguinal white adipose tissue (iWAT) browning. In vivo calcium imaging confirmed vlPAG GABAergic suppression for DIO mice, with corresponding reduction in intrinsic excitability. Single-nucleus RNA sequencing identified transcriptional expression changes in GABAergic cell subtypes in DIO mice, highlighting as of potential importance. Overexpressing CACNA2D1 in vlPAG GABAergic cells of DIO mice rescued enhanced mIPSCs and calcium response, reversed obesity, and therefore presented here as a potential target for obesity treatment.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619925PMC
http://dx.doi.org/10.1126/sciadv.adh2884DOI Listing

Publication Analysis

Top Keywords

dio mice
16
gabaergic cells
12
vlpag gabaergic
12
high-fat diet-induced
8
diet-induced obesity
8
enhanced mipscs
8
obesity
6
gabaergic
5
neural adaption
4
adaption midbrain
4

Similar Publications

Aims: Hypothalamic endoplasmic reticulum stress (ERS) and mitochondrial dysfunction are two important mechanisms involved in the pathophysiology of obesity, which can be reversed by aerobic exercise to improve organ function. Mitofusion 2 (Mfn2), a mitochondrial membrane protein, affects both mitochondrial dynamics and ER morphology. This study explored the contribution of hypothalamic Mfn2 to exercise-induced improvements in energy homeostasis and peripheral metabolism and the underlying mechanisms involved.

View Article and Find Full Text PDF

High-fat diet (HFD) -induced microglial activation contributes to hypothalamic inflammation and obesity, but the mechanisms linking microglia to structural changes remain unclear. This study explored the role of microglia in impairing hypothalamic synaptic plasticity in diet-induced obesity (DIO) mice and evaluated the therapeutic potential of semaglutide (Sema) and minocycline (MI). Six-week-old C57BL/6J mice were divided into low-fat diet (LFD) and HFD groups.

View Article and Find Full Text PDF

Cholesterol (Cho) is commonly used to stabilize nanoliposomes; however, there is controversy on the relationship between Cho and health. In this study, we developed a novel multifunctional nanoliposome utilizing structurally similar sitogluside (SG) and dioscin (Dio) instead of Cho to anchor the phospholipid bilayer and synergistically modulate the membrane properties of the nanoliposome (DPPC or DOPC). The storage and gastrointestinal tract stability experiment demonstrated that the changes of physical and chemical properties, including the significantly reduced size and Dio retention rate of nanoliposomes synergistically modulated by SG and Dio compared to those of SG alone, regulated nanoliposomes.

View Article and Find Full Text PDF

Nesfatin-1 is involved in hyperbaric oxygen-mediated therapeutic effects in high fat diet-induced hyperphagia in mice.

Peptides

December 2024

Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao 266000, China. Electronic address:

Obesity is a worldwide health issue. Effective and safe methods for obesity management are highly desirable. In the current study, hyperbaric oxygen (HBO) treatment was investigated as a potential treatment against obesity-associated hyperphagia and hyperenergy intake.

View Article and Find Full Text PDF

Engrailed1 in Parvalbumin-Positive Neurons Regulates Eye-Specific Retinogeniculate Segregation and Visual Function.

J Neurosci Res

December 2024

State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Institute for Medical and Engineering Innovation, Eye and ENT Hospital, Fudan University, Shanghai, China.

Homeobox transcription factor Engrailed1 (En1) is expressed in the ectoderm and mediates the establishment of retinotectal topography, but its role in eye-specific retinogeniculate segregation and visual function remains unclear. Parvalbumin (PV) neurons, which are widely distributed in the visual pathway, play a crucial role in visual development and function. In this study, we conditionally knocked out En1 gene in PV neurons and found an expansion of the ipsilateral eye projection, while no significant effects were observed in the contralateral eye projection.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!