Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

Biology, Год журнала: 2022, Номер 11(8), С. 1237 - 1237

Опубликована: Авг. 19, 2022

Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and leading indication for transplantation in future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, kidney disease. Aggravating socio-economic impact this complex pathology, routinely feasible diagnostic methodologies effective drugs management are unavailable. The pathophysiology NAFLD, recently defined metabolic (MAFLD), correlated abnormal adipose tissue-liver axis communication because obesity-associated white tissue (WAT) inflammation dysfunction prompt insulin resistance (IR), lipid accumulation (steatosis), non-alcoholic steatohepatitis (NASH), fibrosis. Accumulating evidence links adipokines, cytokine-like hormones secreted by that have immunometabolic activity, pathogenesis progression; however, much uncertainty still exists. Here, current knowledge on roles leptin, adiponectin, ghrelin, resistin, retinol-binding protein 4 (RBP4), visfatin, chemerin, adipocyte fatty-acid-binding (AFABP) taken from preclinical to clinical studies, overviewed. effect therapeutic interventions adipokines' circulating levels covered. Finally, directions address potential adipokines targets biomarkers discussed.

Язык: Английский

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Current Discoveries and Future Implications of Eating Disorders

International Journal of Environmental Research and Public Health, Год журнала: 2023, Номер 20(14), С. 6325 - 6325

Опубликована: Июль 8, 2023

Eating disorders (EDs) are characterized by severe disturbances in eating behaviors and can sometimes be fatal. also associated with distressing thoughts emotions. They conditions affecting physical, psychological, social functions. Preoccupation food, body weight, shape may play an important role the regulation of disorders. Common have three major types: anorexia nervosa (AN), bulimia (BN), binge disorder (BED). In some cases, EDs serious consequences for individual’s physical mental health. These often develop during adolescence or early adulthood affect both males females, although they more commonly diagnosed young adult females. Treatment typically involves a combination therapy, nutrition counseling, medical care. this narrative review, authors summarized what is known discussed future directions that worth exploring emerging area.

Язык: Английский

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Insight into the role of the gut-brain axis in alcohol-related responses: Emphasis on GLP-1, amylin, and ghrelin

Frontiers in Psychiatry, Год журнала: 2023, Номер 13

Опубликована: Янв. 9, 2023

Alcohol use disorder (AUD) contributes substantially to global morbidity and mortality. Given the heterogenicity of this brain disease, available pharmacological treatments only display efficacy in sub-set individuals. The need for additional treatment options is thus substantial goal preclinical studies unraveling neurobiological mechanisms underlying AUD. Although these processes are complex numerous, one system gaining recent attention gut-brain axis. Peptides axis include anorexigenic peptide like glucagon-like peptide-1 (GLP-1) amylin as well orexigenic ghrelin. In animal models, agonists GLP-1 or receptor ghrelin (GHSR) antagonists reduce alcohol drinking, relapse alcohol-seeking. Moreover, three peptides modulate alcohol-related responses (behavioral neurochemical) rodents, suggesting that reduction may involve a suppression alcohol’s rewarding properties. Brain areas participating ability alcohol-mediated behaviors/neurochemistry those important reward. Human support polymorphisms genes encoding pathway associated with agonist decreases drinking overweight patients AUD an inverse GHSR reduces craving. clinical reveal interaction between AUD, should explore more detail.

Язык: Английский

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Neuroendocrinological factors in binge eating disorder: A narrative review

Psychoneuroendocrinology, Год журнала: 2023, Номер 150, С. 106030 - 106030

Опубликована: Янв. 28, 2023

Neuroendocrine mechanisms play a key role in the regulation of eating behavior. In individuals with binge disorder (BED), alterations these signaling hunger and satiety have been observed. It has investigated that may underlie development maintenance compulsive overeating BED. The present narrative review examined current literature related to neurobiological processes involved feeding dysregulation BED aim updating most relevant aspects special attention neuroendocrine signaling. Studies shown both central peripheral endocrine dysfunctions hormones participating homeostatic hedonic pathways Most studies especially focused on orexigenic signals, pointing out existence hyperactivated mechanism promoting hunger. Fewer explored anorexigenic pathways, but findings so far seem suggest an abnormal threshold. Despite this, date, it is unable identify whether are typical pathophysiology or obesogenic pattern due included patients obesity. identification endophenotypes provide new approach aberrant behavior, favoring implementation biological therapeutic targets.

Язык: Английский

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Targeting orexin receptors: Recent advances in the development of subtype selective or dual ligands for the treatment of neuropsychiatric disorders

Medicinal Research Reviews, Год журнала: 2023, Номер 43(5), С. 1607 - 1667

Опубликована: Апрель 10, 2023

Abstract Orexin‐A and orexin‐B, also named hypocretin‐1 hypocretin‐2, are two hypothalamic neuropeptides highly conserved across mammalian species. Their effects mediated by distinct G protein‐coupled receptors, namely orexin receptor type 1 (OX1‐R) 2 (OX2‐R), which share 64% amino acid identity. Given the wide expression of OX‐Rs in different central nervous system peripheral areas several pathophysiological functions they involved, including sleep‐wake cycle regulation (mainly OX2‐R), emotion, panic‐like behaviors, anxiety/stress, food intake, energy homeostasis OX1‐R), both subtypes represent targets interest for many structure–activity relationship (SAR) campaigns carried out pharmaceutical companies academies. However, before 2017 research was predominantly directed towards dual‐orexin ligands, limited chemotypes were investigated. Analytical characterizations, resolved structures OX1‐R OX2‐R complex with agonists antagonists, have improved understanding molecular basis recognition assets medicinal chemists design subtype‐selective ligands. This review is focused on chemistry aspects small molecules acting as dual or subtype selective OX1‐R/OX2‐R antagonists belonging to developed last years, radiolabeled OX‐R ligands imaging. Moreover, pharmacological most studied neuropsychiatric diseases, such sleep, mood, substance use, eating disorders, well pain, been discussed. Poly‐pharmacology applications multitarget considered.

Язык: Английский

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Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila

Cells, Год журнала: 2022, Номер 11(16), С. 2534 - 2534

Опубликована: Авг. 16, 2022

The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis obesity promotes low-grade inflammation peripheral organs the brain contributing to metabolic alterations. mechanisms underlying remain unclear. We investigated if affects striatum using a cohort of control-fed or diet-induced obese (DIO) male mice. tested potential effects specific bacteria on by administrating Akkermansia muciniphila daily placebo DIO showed that are associated with alterations blood–brain barrier identified as novel actor able improve dysregulated behaviors obesity, potentially through decreased activation inflammatory pathways lipid-sensing ability striatum. These results open new field research suggest microbes can be considered an innovative therapeutic approach attenuate This study provides substance for further investigations muciniphila-mediated improvements other neuropsychiatric disorders.

Язык: Английский

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Investigating the role of the central melanocortin system in stress and stress-related disorders

Pharmacological Research, Год журнала: 2022, Номер 185, С. 106521 - 106521

Опубликована: Окт. 20, 2022

The melanocortinergic neural circuit, known for its influence on energy expenditure and feeding behavior, also plays a role in stress stress-induced psychiatric disorders, including anxiety depression. major contribution is given by the melanocortin-4 receptor (MC4R) subtype, highly expressed brain regions involved control of responses. Furthermore, MC4R appears to profoundly affect activity hypothalamic-pituitary-adrenal (HPA) axis, it has been highlighted functional anatomical interaction with corticotropin-releasing factor (CRF), an important mediator stress-related behaviors. agonists seem exacerbate stress-inducing anxiety- depressive-like while antagonists have demonstrated mitigate such as shown several preclinical behavioral tests. evidence collected present review suggests that melanocortin system, through MC4R, could possibly modulate responses stress, suggesting use possible novel treatment depression induced stress.

Язык: Английский

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Association and interaction of the MC4R rs17782313 polymorphism with plasma ghrelin, GLP-1, cortisol, food intake and eating behaviors in overweight/obese Iranian adults

BMC Endocrine Disorders, Год журнала: 2022, Номер 22(1)

Опубликована: Сен. 19, 2022

Abstract Background Recent studies have shown that obesity is largely influenced by heredity and created the interactions between several genes environmental behavioral factors. This study aimed to examine association variant rs17782313 near melanocortin-4 receptor (MC4R) gene hormonal factors then evaluated MC4R with on obesity. Methods cross-sectional included 403 subjects, overweight and/or obesity, aged 20–50 years from Iran. The data were measured PCR–RFLP method. Dietary intake, physical activity, stress, anxiety, depression, appetite emotional eating assessed using validated questionnaires. Ghrelin, glucagon-like peptide-1 cortisol radioimmunoassay in plasma samples. Participants also divided into three groups based genotype BMI. Results After adjustment for age, gender, energy intake PA, significant associations observed food appetite, eating, stress activity ( p ˂0.05). Also, fat p-interaction = 0.002), protein 0.01), 0.02), 0.04), ghrelin 0.03), 0.04) terms of Conclusion Interactions CC high intakes energy, too much levels probably can an effect BMI overweight/obese subjects.

Язык: Английский

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Neuropeptides Modulate Feeding via the Dopamine Reward Pathway

Neurochemical Research, Год журнала: 2023, Номер 48(9), С. 2622 - 2643

Опубликована: Май 26, 2023

Язык: Английский

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Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor

Journal of Medicinal Chemistry, Год журнала: 2022, Номер 65(4), С. 3098 - 3118

Опубликована: Фев. 14, 2022

Ghrelin is an octanoylated peptide acting by the activation of growth hormone secretagogue receptor, namely, GHS-R1a. The involvement ghrelin in several physiological processes, including stimulation food intake, gastric emptying, body energy balance, glucose homeostasis, reduction insulin secretion, and lipogenesis validates considerable interest GHS-R1a as a promising target for treatment numerous disorders. Over years, ligands have been identified some them extensively studied clinical trials. recently resolved structures bound to or potent provided useful information design new drugs. This perspective focused on development recent nonpeptide small molecules agonists, antagonists, inverse bearing classical molecular scaffolds, well radiolabeled developed imaging. Moreover, pharmacological effects most discussed.

Язык: Английский

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