generation-human-cardiac-organoids-from-embryonic-stem-cells-via

Generation of Human Cardiac Organoids from Embryonic Stem Cells via Stepwise Mesoderm Induction and 3D Self-organization

Human embryonic stem cell (hESC)-derived cardiac organoids are multicellular three-dimensional (3D) structures that recapitulate key aspects of early ...

southwest medical university

 Enhancing white adipose tissue (WAT) browning combats obesity. The RIIβ subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIβ gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored.  This study investigates the mechanisms underlying WAT browning in RIIβ-KO mice. Genetic approaches such as β3-adrenergic receptors (β3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 , while AAV-shRNAs were used for the same purpose .  We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIβ-KO mice. The WAT browning can be dampened by βARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIβ-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, βAR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally,  knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity.  The βAR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

βAR-mTOR-lipin1 pathway mediates PKA-RIIβ deficiency-induced adipose browning.

Hypothalamic GABAergic neurons are important in regulating metabolic homeostasis and energy balance. Serving as critical integrators of catabolic and anabolic processes, these neurons orchestrate a broad spectrum of metabolic functions, including feeding, nutrient metabolism, fluid homeostasis, basal metabolism, thermoregulation, and circadian rhythms. Recent advances in neuroscience have facilitated a deeper exploration of the role of hypothalamic GABAergic neurons in metabolic regulation. Emerging research has uncovered key mechanisms through which these neurons modulate energy balance and maintain metabolic balance. These findings not only enhance our understanding of obesity and related metabolic disorders but also underscore the link between hypothalamic dysfunction and prevalent metabolic diseases such as obesity and type 2 diabetes. This review summarizes the latest advancements in our understanding of the role of hypothalamic GABAergic neurons in metabolic regulation. It aims to elucidate the neural and molecular mechanisms underlying hypothalamic control of metabolism, offering new perspectives for the diagnosis and treatment of metabolic disorders.

Article	Year
βAR-mTOR-lipin1 pathway mediates PKA-RIIβ deficiency-induced adipose browning. Theranostics\| PubMed ID: 39267778	2024
Hypothalamic GABAergic neurons: their roles in health and metabolic diseases. Frontiers in endocrinology\| PubMed ID: 40130157	2025

Bingwei Wang

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