Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines

Aging, Год журнала: 2023, Номер unknown

Опубликована: Июнь 29, 2023

Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, the relationship between these is bidirectional. The association depression highly co-morbid tends to significantly exacerbate metabolic related depressive symptoms. However, neural mechanism under mutual control of largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain vivo homeostatic regulation link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation well neuroendocrine regulators energy metabolism including adipocytokines lipokines. In addition, summarizes potential future treatments for raises several questions need be answered research. will provide a comprehensive description localization biological connection better understand co-morbidity depression.

Язык: Английский

---

Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 19, 2023

Abstract Accumulation of α-synuclein into toxic oligomers or fibrils is implicated in dopaminergic neurodegeneration Parkinson’s disease. Here we performed a high-throughput, proteome-wide peptide screen to identify protein-protein interaction inhibitors that reduce oligomer levels and their associated cytotoxicity. We find the most potent inhibitor disrupts direct between C-terminal region CHarged Multivesicular body Protein 2B (CHMP2B), component Endosomal Sorting Complex Required for Transport-III (ESCRT-III). show impedes endolysosomal activity via this interaction, thereby inhibiting its own degradation. Conversely, restores function decreases multiple models, including female male human cells harboring disease-causing mutations. Furthermore, protects neurons from α-synuclein-mediated degeneration hermaphroditic C. elegans preclinical disease models using rats. Thus, α-synuclein-CHMP2B potential therapeutic target neurodegenerative disorders.

Язык: Английский

---

Dietary Fat Modulation of Gut Microbiota and Impact on Regulatory Pathways Controlling Food Intake

Nutrients, Год журнала: 2023, Номер 15(15), С. 3365 - 3365

Опубликована: Июль 28, 2023

Obesity is a multifactorial disease that continues to increase in prevalence worldwide. Emerging evidence has shown the development of obesity may be influenced by taxonomic shifts gut microbiota response consumption dietary fats. Further, these alterations have been promote important changes satiation signals including hormones (leptin, ghrelin, GLP-1, peptide YY and CCK) orexigenic anorexigenic neuropeptides (AgRP, NPY, POMC, CART) influence hyperphagia therefore obesity. In this review, we highlight mechanisms which can both locally gastrointestinal tract via microbiota-gut-brain communication. Then, describe effects interventions associated on satiety through microbiota-dependent mechanisms. Lastly, present optimizing therapies prebiotics, probiotics, synbiotics weight loss surgery help restore beneficial enhancing reduce subsequent Overall, better understanding fats induce taxonomical their impact signaling pathways will develop more targeted therapeutic delaying onset furthering its treatment.

Язык: Английский

---

Genome-wide variation study and inter-tissue communication analysis unveil regulatory mechanisms of egg-laying performance in chickens

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 16, 2024

Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study hens with distinct egg production, to detect hub candidate genes construct molecular networks contributing egg-laying phenotypic differences. We identifiy three as facilitators: TFPI2, which promotes GnRH secretion hypothalamic neuron cells; CAMK2D, FSHβ LHβ pituitary OSTN, granulosa cell proliferation synthesis sex steroid hormones. reveal key endocrine factors involving production by inter-tissue crosstalk analysis, demonstrate that both hepatokine, APOA4, an adipokine, ANGPTL2, could increase communication hypothalamic-pituitary-ovarian axis. Together, These results coordinative regulation chicken provide insights avian reproductive regulation. important phenotype for breeding chicken. Here, authors explore regulatory driving differences egg-laying, identify laying-related variants factors.

Язык: Английский

---

The ARCCRABP1 neurons play a crucial role in the regulation of energy homeostasis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 8, 2025

Recent single-cell RNA sequencing study suggested that CRABP1 expressing neurons in the arcuate nucleus (ARCCRABP1 neurons) were a distinct group of neurons. However, physiological role ARCCRABP1 remains unexplored. Here, we demonstrated played crucial regulation energy homeostasis male mice. Ablation resulted obesity and diabetic phenotype By employing chemogenetic or optogenetic manipulation techniques, inhibition activation an increase decrease food intake, respectively. The axon terminals from these project to several brain regions implicated feeding such as PVH, BNST, PBN, NTS. Optogenetic axons within significant alterations intake behavior Furthermore, electrophysiological studies induces depolarization POMC hypothalamus. hormone stimulation showed most respond insulin. Collectively, our findings demonstrate represent neuronal subtype involved regulation. AgRP hypothalamus widely known regulate balance. authors show are identified new player influencing appetite metabolism.

Язык: Английский

---

Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli

Cell Reports, Год журнала: 2020, Номер 33(6), С. 108362 - 108362

Опубликована: Ноя. 1, 2020

Motivational states consist of cognitive, emotional, and physiological components controlled by multiple brain regions. An integral component this neural circuitry is the bed nucleus stria terminalis (BNST). Here, we identify that neurons within BNST express gene prepronociceptin (PnocBNST) modulate rapid changes in arousal occur upon exposure to motivationally salient stimuli. Using vivo two-photon calcium imaging, find PnocBNST neuronal responses directly correspond with increases pupillary size when mice are exposed aversive rewarding odors. Furthermore, optogenetic activation these anxiety-like behaviors but does not induce approach, avoidance, or locomotion. These findings suggest excitatory encode anxiety states. Further histological, electrophysiological, single-cell RNA sequencing data reveal composed genetically anatomically identifiable subpopulations may differentially tune motivational

Язык: Английский

---

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

Science Translational Medicine, Год журнала: 2021, Номер 13(590)

Опубликована: Апрель 21, 2021

Pharmacological manipulation of the melanocortin-3 receptor bidirectionally controls feeding, providing a therapeutic target for eating disorders.

Язык: Английский

---

Brain circuits for promoting homeostatic and non-homeostatic appetites

Experimental & Molecular Medicine, Год журнала: 2022, Номер 54(4), С. 349 - 357

Опубликована: Апрель 26, 2022

Abstract As the principal means of acquiring nutrients, feeding behavior is indispensable to survival and well-being animals. In response energy or nutrient deficits, animals seek consume food maintain homeostasis. On other hand, even when are calorically replete, non-homeostatic factors, such as sight, smell, taste palatable food, environmental cues that predict can stimulate behavior. These homeostatic factors have traditionally been investigated separately, but a growing body literature highlights these work synergistically promote Furthermore, recent breakthroughs in cell type-specific circuit-specific labeling, recording, manipulation techniques markedly accelerated discovery well-defined neural populations underlying appetite control, well overlapping circuits contribute both types appetite. This review aims provide an update on our understanding circuit mechanisms for promoting appetites, focusing function recently identified, genetically defined types.

Язык: Английский

---

A critical update on the l eptin‐melanocortin system

Journal of Neurochemistry, Год журнала: 2023, Номер 165(4), С. 467 - 486

Опубликована: Янв. 17, 2023

Abstract The discovery of leptin in 1994 was an “eureka moment” the field neurometabolism that provided new opportunities to better understand central control energy balance and glucose metabolism. Rapidly, a prevalent model emerged pro‐opiomelanocortin (POMC) neurons were key promoting leptin's anorexigenic effects arcuate nucleus hypothalamus (ARC) region for regulation homeostasis. While this inspired many important discoveries, growing body literature indicates is now outdated. In review, we re‐evaluate hypothalamic leptin–melanocortin light recent advances directly tackle previous assumptions, with particular focus on ARC. We discuss how segregated heterogeneous these are, examine development modern approaches allowing spatiotemporal, intersectional, chemogenetic manipulations melanocortin has allowed definition complexity system. review importance regulating homeostasis, but not food intake, through direct actions ARC POMC neurons. further highlight non‐POMC, GABAergic mediate influence image

Язык: Английский

---

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 25, 2024

Abstract Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action the mammalian brain remains unclear due to lack high-resolution approaches detect this neuropeptide appropriate spatial temporal resolution. Here we develop characterize NOPLight, genetically encoded sensor that sensitively reports changes endogenous release. We characterized affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, potential interaction intracellular signal transducers NOPLight vitro. Its functionality was established acute slices by exogeneous application chemogenetic induction release from PNOC neurons. In vivo studies fibre photometry enabled direct recording binding exogenous receptor ligands, as well detection within paranigral ventral tegmental area (pnVTA) during natural behaviors activation summary, show here can be used dynamics tissue freely behaving animals.

Язык: Английский

---