Obesity and Obesity-Related Disorders-Editorial.

Obesity and obesity-related complications, including various metabolic diseases and cancers, are significant health problems in developed and developing countries [...].

Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms.

Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1ß) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.

The multifaceted functions of NFE2L1 in metabolism and associated disorders.

Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as Nrf1) is a crucial member of the CNC-bZIP subfamily of transcription factors expressed ubiquitously throughout our body. Recent findings have revealed its association with various metabolic processes, encompassing glucose, lipid, and protein metabolism. In the realm of glucose metabolism, NFE2L1 exerts regulatory control by modulating pancreatic ß cells and insulin production. It also influences glucose metabolism in liver and the insulin sensitivity of adipose tissue. Regarding lipid metabolism, NFE2L1 governs this process by influencing the expression of specific adipogenic and lipolysis genes in both liver and adipose tissue. Additionally, NFE2L1 regulates specific lipids, such as cholesterol. These involvements underlie various manifestations of NFE2L1 deficiency such as adipocyte hypertrophy, inflammation, and steatohepatitis. In the realm of protein metabolism, NFE2L1 serves as a major transcription factor regulating the 26S proteasome genes expression, which dysfunction has been related with multiple diseases including neurodegenerative diseases, cancers, autoimmune conditions, etc. In this comprehensive review, we summarize the diverse roles that NFE2L1 plays in glucose, lipid, and protein metabolism, as well as its impact on diseases related to these metabolic processes.

FNIP1: A key regulator of mitochondrial function.

Folliculin interacting protein 1 (FNIP1), a novel folliculin interacting protein 1, is a key regulatory factor for mitochondrial function. FNIP1 mainly responds to energy signal transduction through physical interactions with 5'-AMP activated protein kinase (AMPK). Simultaneously, it affects the transcription of mitochondria-associated genes by regulating the lysosomal localization of mechanistic target of rapamycin kinase (mTORC1). This article takes FNIP1 as the core and first introduces its involvement in the development of B cells and invariant natural killer T (iNKT) cells, muscle fiber type conversion, and the thermogenic remodeling of adipocytes by regulating mitochondrial function. In addition we discuss the detailed impact of upstream regulatory factors of FNIP1 on its function. Finally, the impact of FNIP1 on the prognosis and treatment of clinically related metabolic diseases is summarized, aiming to provide a new theoretical basis and treatment plans for the diagnosis and treatment of such diseases.

Molecular insights into Sertoli cell function: how do metabolic disorders in childhood and adolescence affect spermatogonial fate?

Male infertility is a major public health concern globally with unknown etiology in approximately half of cases. The decline in total sperm count over the past four decades and the parallel increase in childhood obesity may suggest an association between these two conditions. Here, we review the molecular mechanisms through which obesity during childhood and adolescence may impair future testicular function. Several mechanisms occurring in obesity can interfere with the delicate metabolic processes taking place at the testicular level during childhood and adolescence, providing the molecular substrate to hypothesize a causal relationship between childhood obesity and the risk of low sperm counts in adulthood.

Roles of lipid droplets and related proteins in metabolic diseases.

Lipid droplets (LDs), which are active organelles, derive from the monolayer membrane of the endoplasmic reticulum and encapsulate neutral lipids internally. LD-associated proteins like RAB, those in the PLIN family, and those in the CIDE family participate in LD formation and development, and they are active players in various diseases, organelles, and metabolic processes (i.e., obesity, non-alcoholic fatty liver disease, and autophagy). Our synthesis on existing research includes insights from the formation of LDs to their mechanisms of action, to provide an overview needed for advancing research into metabolic diseases and lipid metabolism.

The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Lipid Droplet-Mitochondria Contacts in Health and Disease.

The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining cellular homeostasis. Lipid droplets (LDs), once considered inert storage depots for neutral lipids, are now recognized as dynamic organelles critical in lipid metabolism and energy regulation. Mitochondria, the powerhouses of the cell, play a central role in energy production, metabolic pathways, and redox signaling. The physical and functional contacts between LDs and mitochondria facilitate a direct transfer of lipids, primarily fatty acids, which are crucial for mitochondrial ß-oxidation, thus influencing energy homeostasis and cellular health. This review highlights recent advances in understanding the mechanisms governing LD-mitochondria interactions and their regulation, drawing attention to proteins and pathways that mediate these contacts. We discuss the physiological relevance of these interactions, emphasizing their role in maintaining energy and redox balance within cells, and how these processes are critical in response to metabolic demands and stress conditions. Furthermore, we explore the pathological implications of dysregulated LD-mitochondria interactions, particularly in the context of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and their potential links to cardiovascular and neurodegenerative diseases. Conclusively, this review provides a comprehensive overview of the current understanding of LD-mitochondria interactions, underscoring their significance in cellular metabolism and suggesting future research directions that could unveil novel therapeutic targets for metabolic and degenerative diseases.

Protein Tyrosine Phosphatase 1B (PTP1B): A Comprehensive Review of Its Role in Pathogenesis of Human Diseases.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer's disease, Parkinson's disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.

Molecular mechanisms and drug therapy of metabolism disorders in psoriasis.

Psoriasis is a prevalent skin disease affecting approximately 1%-3% of the population and imposes significant medical, social and economic burdens. Psoriasis involves multiple organs and is often complicated with obesity, diabetes, dyslipidemia, and hypertension. Because of the benefits of lipid-lowering agents and antidiabetic medications for psoriasis, metabolic abnormalities possibly play a pathogenic role in psoriasis.This review focuses on the impacts of a variety of metabolic disorders on psoriasis and the underlying mechanisms.In psoriasis, enhanced glycolysis, glutamine metabolism and altered fatty acid composition in the psoriatic lesion and plasma result in the excessive proliferation of keratinocytes and secretion of inflammatory cytokines. Altered metabolism is associated with the activation of MTORC signaling pathway and transcription factors such as HIF and S6K1. Therefore, MTORC1 can be a target for the treatment of psoriasis. Additionally, there are diabetes drugs and lipid-lowering drugs including TZDs, GLP-1 RAs, Metformin, statins and fibrates, which improve both metabolic levels and psoriasis symptoms.

miRNA and leptin signaling in metabolic diseases and at extreme environments.

The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases.

Body Composition in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease: Impact of Body Surface Area.

BACKGROUND/AIM: To examine the relationship between the body surface area (BSA) and body composition in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, 2,141 men and 986 women). MATERIALS AND METHODS: BSA and body composition parameters were examined. RESULTS: The median body mass index (BMI) was 25.0 kg/m2 for both men and women (p=0.7754). The median body surface area (BSA) was 1.854 m2 for men and 1.618 m2 for women (p<0.0001). In men, the median fat mass was 17.7 kg, whereas in women, it was 22.1 kg (p<0.0001). Additionally, the median fat-free mass was 55.4 kg in men and 39.3 kg in women (p<0.0001).). In male cases, BSA significantly correlated with fat mass (r=0.82, p<0.0001) and fat-free mass (r=0.95, p<0.0001). In female cases, BSA significantly correlated with fat mass (r=0.87, p<0.0001) and fat-free mass (r=0.94, p<0.0001). CONCLUSION: BSA could be a useful marker for the estimation of body composition in patients with MASLD.

Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options.

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and, finally, "metabolic dysfunction-associated steatotic liver disease" (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut-liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.

mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.

The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging. Given its extensive biological impact, mTOR signaling is a prime therapeutic target for addressing these complex conditions. The development of mTOR inhibitors has proven advantageous in numerous research domains. This review delves into the significance of mTOR signaling, highlighting the critical components of this intricate network that contribute to disease. Additionally, it addresses the latest findings on mTOR inhibitors and their clinical implications. The review also emphasizes the importance of developing more effective next-generation mTOR inhibitors with dual functions to efficiently target the mTOR pathways. A comprehensive understanding of mTOR signaling will enable the development of effective therapeutic strategies for managing diseases associated with mTOR dysregulation.