Signaling pathways in obesity: mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 28, 2022

Abstract Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases risk of several diseases, such as type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver linked to lower life expectancy. Although lifestyle intervention (diet exercise) has remarkable effects on weight management, achieving long-term success at loss extremely challenging, prevalence continues rise worldwide. Over past decades, pathophysiology been extensively investigated, an increasing number signal transduction pathways have implicated obesity, making it possible fight more effective precise way. In this review, we summarize recent advances pathogenesis from both experimental clinical studies, focusing signaling their roles regulation food intake, glucose homeostasis, adipogenesis, thermogenesis, inflammation. We also discuss current anti-obesity drugs, well compounds trials, that target these signals. The evolving knowledge may shed light future direction research, move into new era precision medicine.

Language: Английский

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MC3R links nutritional state to childhood growth and the timing of puberty

Nature, Journal Year: 2021, Volume and Issue: 599(7885), P. 436 - 441

Published: Nov. 3, 2021

Language: Английский

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Targeting the central melanocortin system for the treatment of metabolic disorders

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(9), P. 507 - 519

Published: June 26, 2023

Language: Английский

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Efficacy and cytotoxicity of engineered ferromanganese-bearing sludge-derived biochar for percarbonate-induced phthalate ester degradation

Journal of Hazardous Materials, Journal Year: 2021, Volume and Issue: 422, P. 126922 - 126922

Published: Aug. 18, 2021

Language: Английский

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Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 22, 2023

Abstract Alpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their tissue specific expression involvement melanocyte homeostasis. However, role prevention treatment of is still debated controversial. Although a large body evidence supports α-MSH preventing development, some preclinical findings suggest that the downstream signalling may promote immune escape cancer resistance therapy. Additionally, metastatic both MC1R reported be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition V600E mutant tumours) has shown enhance this phenomenon. Collectively, these data targeting could serve an approach melanoma. In review, we explore molecular biology with particular emphasis into tumor-related properties, whilst elaborating experimental currently available regarding interplay between α-MSH/MC1R axis, antitumor strategies.

Language: Английский

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Chemotherapy-induced gastrointestinal toxicity: Pathogenesis and current management

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 216, P. 115787 - 115787

Published: Sept. 4, 2023

Language: Английский

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Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 10, 2024

Abstract Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5–7 months comprises weeks hypometabolic, hypothermic torpor interspersed with 24–48-h an active-like interbout arousal (IBA) state. We show that squirrels, who endure entire season without food, have negligible hunger during IBAs. These exhibit reversible inhibition hypothalamic feeding center, such arcuate nucleus neurons reduced sensitivity to orexigenic anorexigenic effects ghrelin leptin, respectively. However, infusion thyroid hormone IBA is sufficient rescue anorexia. Our results reveal deficiency underlies anorexia demonstrate functional flexibility center.

Language: Английский

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Translational advances of melanocortin drugs: Integrating biology, chemistry and genetics

Seminars in Immunology, Journal Year: 2022, Volume and Issue: 59, P. 101603 - 101603

Published: Jan. 1, 2022

Melanocortin receptors have emerged as important targets with a very unusual versatility, their widespread distribution on multiple tissues (e.g. skin, adrenal glands, brain, immune cells, exocrine glands) together the variety of physiological processes they control (pigmentation, cortisol release, satiety mechanism, inflammation, secretions), place this family genuine therapeutic for many disorders. This review focuses in journey development melanocortin from discovery existence early 1990 s to approval first few drugs class. Two major areas characterise current state drug development: role obesity, recently culminated setmelanotide, and potential treatment chronic inflammatory autoimmune diseases like rheumatoid arthritis, sclerosis or fibrosis. The pro-resolving nature these offers advantage acting by mimicking way our body naturally resolves expecting fewer side effects more balanced (i.e. non-immunosuppressive) response them. Here we also approaches followed design novel compounds, importance GPCR process development, value, challenges successes, implementation precision medicine through incorporation genetics advances.

Language: Английский

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KNDy neurons as the GnRH pulse generator: Recent studies in ruminants

Peptides, Journal Year: 2023, Volume and Issue: 164, P. 171005 - 171005

Published: March 27, 2023

Language: Английский

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Miniature microscopes for manipulating and recording in vivo brain activity

Microscopy, Journal Year: 2021, Volume and Issue: 70(5), P. 399 - 414

Published: July 20, 2021

Here we describe the development and application of miniature integrated microscopes (miniscopes) paired with microendoscopes that allow for visualization manipulation neural circuits in superficial subcortical brain regions freely behaving animals. Over past decade miniscope platform has expanded to include simultaneous optogenetic capabilities, electrically-tunable lenses enable multi-plane imaging, color-corrected optics, an data acquisition streamlines multimodal experiments. Miniscopes have given researchers unprecedented ability monitor hundreds thousands genetically-defined neurons from weeks months both healthy diseased animal brains. Sophisticated algorithms take advantage constrained matrix factorization background estimation reliable cell identification, greatly improving reliability scalability source extraction large imaging datasets. Data generated miniscopes empowered investigate circuit underpinnings a wide array behaviors cannot be studied under head-fixed conditions, such as sleep, reward seeking, learning memory, social behaviors, feeding. Importantly, broadened our understanding how can go awry models progressive neurological disorders, Parkinson's disease. Continued development, including record multiple populations cells simultaneously, along continued integration techniques electrophysiology, will deeper into underlie complex naturalistic behavior.

Language: Английский

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