The neonatal period is crucial for calf development, particularly for immune acquisition through colostrum intake, this study aimed to assess the energy metabolism and inflammatory response. Ten Italian Simmental calves were monitored from birth to 60 days of age, with blood samples taken at birth (0 d) to weaning. Plasma concentrations of UCP-1, leptin, TNF-α, IL-1β, IL-6, lipids, triglycerides, and total cholesterol were measured. Results showed significant dynamic changes (P < 0.05) in all parameters and showing an increasing trend from birth to the 60 d of age in investigated calves. The plasma leptin levels were positively correlated with the concentration of UCP-1 (r = 0.37, P = 0.0003), total lipids (r = 0.47, P < 0.0001), triglycerides (r = 0.53, P < 0.0001), total cholesterol (r = 0.38, P = 0.0002), and negatively correlated with TNF-α (r = -0.24, P 0.02). UCP-1 was positively correlated with the levels of total lipids (r = 0.31, P = 0.003), triglycerides (r = 0.29, P = 0.005), and IL-1β (r = 0.29, P = 0.005) in calves throughout the monitoring period. IL-6 values positively correlated with total lipids (r = 0.36; P = 0.0004), triglycerides (r = 0.37; P = 0.0003), and total cholesterol (r = 0.21; P = 0.04) in calves throughout the monitoring period. These findings suggest that lipid metabolism and inflammatory responses undergo significant changes as calves adapt to the neonatal phase and transition to solid food, with nutritional shifts playing a key role in metabolic and immune system development.

Type 2 diabetes mellitus (T2DM) develops primarily from obesity as leptin (LEP) functions as an essential adipokine that controls metabolic regulation, energy balance activities, and glucose maintenance. The T2DM and obesity susceptibility traits are believed to be affected by genetic variations in the leptin receptor gene (LEPR), disrupting LEP signaling mechanisms. This case-control study investigates the association of these variants with T2DM risk in a Southeastern Iranian population.

A case-control study was conducted involving 450 T2DM patients and 450 matched healthy controls from Zahedan. Genomic DNA for this study was isolated from peripheral blood samples, and genotyping for the specified LEPR rs1137100, rs1137101, and rs1805094 polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Computational analysis created a gene-gene interaction network, highlighting LEPR as a central hub gene and detailing its interactions with related genes.

Genetic models, such as codominant heterozygous (p-value = 0.009), dominant (p-value = 0.006), recessive (p-value = 0.008), and allelic (p-value = 0.011), all showed that the rs1137100 (A/G) polymorphism lowered the risk of T2DM. Several genetic models linked polymorphisms at the rs1137101 (G/A) and rs1805094 (G/C) loci to a higher risk of T2DM: The genetic models that were looked at were polymorphism rs1137101 (G/A) in codominant Homozygous (p-value = 0.031) and recessive (p-value = 0.028), as well as polymorphism rs1805094 (G/C) in codominant heterozygous (p-value = 0.009), dominant (p-value = 0.001), excess (p-value = 0.008), and allelic (p-value = 0.001). The research demonstrated a profound linkage disequilibrium (LD) among studied variants, especially in the LEPR haplotypes and across various blocks, with differing levels of association strength. The gene-gene interaction network for the LEPR gene highlights its strong associations with several key regulatory genes: LEP, PTPN11, STAT3, POMC, JAK2, IL6, and SOCS3.

We found a significant correlation between LEPR gene polymorphisms and the risk of T2DM, highlighting the prominent role of genetic factors in developing such a metabolic disorder. By elucidating the association between LEPR variations and susceptibility to T2DM, our findings enhance the understanding of molecular mechanisms involved in endocrine dysregulation and highlight the importance of including genetic profiling in clinical practice.

Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin's role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.

Appetite loss is a common clinical condition in older adulthood, but how this condition associates with biological aging remains unknown. The present study aims to examine the associations of biological aging markers with appetite loss in community-dwelling people aged 21 to 102 years. This retrospective case-control study used baseline data from the INSPIRE-T cohort in Toulouse, France. Each of the 49 cases with appetite loss was sex- and age-matched to two controls without appetite loss (n = 147; median age of 79 years, interquartile range: 19.5; 67% women). Appetite loss was assessed using a single yes-no question from the World Health Organization´s Integrated Care for Older People screening tool. Biomarkers (first- and second-generation DNA methylation-based epigenetic clocks [Horvath, Hannum, PhenoAge, and GrimAge], the inflammatory aging clock iAge, and Adenosine triphosphatase inhibitory factor 1-IF1) were derived from blood samples. Logistic regression analyzed the associations of these markers with appetite loss. In fully adjusted models, accelerated aging using GrimAge was the only biomarker associated with appetite loss (Odds Ratio = 1.21, 95% Confidence Interval: 1.03, 1.43). When stratified by age (≤ 65 years vs. > 65 years) and sex, this association remained significant only in individuals over 65 years and men. Future research is needed to explore the potential mechanisms involved, as well as how other biological drivers of aging (e.g., cell senescence, deregulated nutrient sensing) relate to appetite loss.

This study evaluated aqueous Vernonia amygdalina leaf extract in drinking water as a mitigation strategy against Aflatoxin B1-induced toxicity in broilers, focusing on performance, haematology, serum biochemistry, pro-inflammatory cytokines, cellular stress markers, and liver histology. Two hundred and forty (240) day-old chicks (mixed sex), of the Cobb 500 breed were divided into four groups: control (CONT), AFB1-exposed (AFLB1), and two treatment groups (VE1AF and VE2AF) receiving 0.5 mg/kg AFB1 and Vernonia amygdalina aqueous extract at 1 g/L and 2 g/L, respectively. At 42 days, VE1AF and VE2AF chickens showed higher (P < 0.05) final weights and weight gains than CONT and AFLB1 groups. The red blood cells, packed cell volume, haemoglobin, and white blood cell counts were higher (P < 0.05) in CONT, VE1AF, and VE2AF groups compared to AFLB1. Mean cell volume, and mean cell haemaoglobin were higher (P < 0.05) in AFLB1 and VE2AF. Serum analysis revealed lower (P < 0.05) total protein, globulin, and albumin in AFLB1, which were restored by the extract. The tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, were elevated (P < 0.05) in AFLB1 but reduced in VE1AF and VE2AF. The heat shock protein 70, 8-hydroxy-2'-deoxyguanosine and adiponectin levels were higher (P < 0.05) in AFLB1, but were normalized by the extract in VE1AF and VE2AF. Leptin and triiodothyronine levels were significantly (P < 0.05) better in VE1AF and VE2AF, compared to AFLB1. Liver histology showed reduced inflammation in VE1AF and VE2AF, with near-normal hepatic architecture. In conclusion, Vernonia amygdalina leaf extract effectively counteracts AFB1 toxicity, enhancing overall health and performance in broiler chickens.

Parkinson's disease (PD) is the second most commonneurodegenerative disease, characterized bybradykinesia, resting tremor, stiffness, and postural instabilityresulting due to the progressive loss ofdopaminergic neurons in the substantia nigra (SN). The pathophysiology of PDis extremely complex and involves mitochondrial dysfunction, oxidative stress, neuroinflammation, and disruption of protein homeostasis. Its progression is affected by both environmental and genetic factors, including mutations in the alpha-synuclein (SNCA), PTEN-induced kinase 1 (PINK1), and leucine-rich repeat kinase 2 (LRRK2) genes. Leptin, primarily secreted by the adipose tissue, has garnered significant interest for its involvement in neuroprotective mechanisms and potential role in the progression of PD. Its receptors located in the SN and hippocampus region indicate its role in neuronal survival and function. The role of leptin in the central nervous system (CNS) highlights its impact on neuroinflammation, oxidative stress, and synaptic plasticity. Recent studies indicate that through activation of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3) and the phosphoinositide 3 kinase (PI3 K)/Akt pathways, leptin may exert a neuroprotective effect by preventing the degeneration of dopaminergic neurons, which marked as the hallmark in the pathophysiology of PD. Additionally, leptin's interaction with neurotrophic factors and its ability to enhance synaptic plasticity highlight its vital role in preserving neuronal health. This review summarizes the role of leptin as a neuroprotective mechanism in PD and explores its potential role as a therapeutic target for treatment to enhance neuroprotection and clinical outcome, by addressing the neurodegenerative characteristics associated with PD.

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations and systemic inflammation. The interaction between the metabolic and inflammatory pathways plays a key role in disease progression, with leptin and insulin emerging as pivotal metabolic regulators. Leptin, an adipokine that regulates energy homeostasis, and insulin, the primary regulator of glucose metabolism, are both altered in COPD patients. This narrative review provides an in-depth examination of the roles of leptin and insulin in COPD pathogenesis, focusing on the molecular mechanisms through which these metabolic regulators interact with inflammatory pathways and how their dysregulation contributes to a spectrum of extrapulmonary manifestations. These disturbances not only exacerbate COPD symptoms but also increase the risk of comorbidities such as metabolic syndrome, diabetes, cardiovascular disease, or muscle wasting. By exploring the underlying mechanisms of leptin and insulin dysregulation in COPD, this review underscores the significance of the metabolic-inflammatory axis, suggesting that restoring metabolic balance through leptin and insulin modulation could offer novel therapeutic strategies for improving clinical outcomes.

Sepsis is a severe and life-threatening disease involving multiple risk factors. Leptin has been suggested to play a role in modulating the inflammatory response in sepsis and improving outcomes; however, there are conflicting results regarding the outcome of sepsis. The present study aims to clarify the expression of leptin in patients with sepsis, and its association with other cytokines.

The retrospective study enrolled 165 adults with sepsis from medical intensive care units (ICU)s, and collected leptin, glucose levels, and cytokines such as IL-6, IL-1RA, IL-10, IL-17, TNF-α, IFN-γfor analysis. Leptin levels were divided into three groups based on concentration: Low (≤ 3.78 ng/mL), Medium (3.78 < leptin ≤ 23.2 ng/mL), and High (> 23.2 ng/mL). Survival curve analysis and comparisons among groups were performed. A subgroup analysis by sex (male and female) was also conducted. Finally, a multiple-factor logistic regression model was used to evaluate the interaction between leptin and other factors.

The high leptin groups were the oldest (low vs. medium vs. high: 60 vs. 66 vs. 78, p < 0.0001) and had the highest body mass index (BMI) (19.8 vs. 23.9 vs. 24.2, p < 0.0001), the highest percentages of women (28.6 vs. 34.1 vs. 65.9 p = 0.001), and the most comorbidities (1 vs. 1 vs. 2, p = 0.001). After controlling IL-6, day 1 leptin had a trend associated with lower mortality in the hospital (β = 0.984, p = 0.062). The highest IL-6 group had a significantly higher mortality rate among three IL-6 level patients (p = 0.015), but in the high leptin subgroup analysis, the significant effect of high IL-6 on mortality disappeared. Besides, the subgroup analysis of men, the high leptin group had a trend of better survival than the medium and low leptin groups.

High leptin levels may mitigate the adverse prognostic impact of elevated IL-6 on septic mortality. At comparable IL-6 levels, leptin could serve as a predictor of septic outcomes. Leptin might act as a protective factor in men. Future research should explore leptin's role in IL-6-mediated inflammation and its potential protective effect in high IL-6 sepsis cases.

Early life stress (ELS) is a significant risk factor for the development of mood and metabolic disorders later in life, which are often in comorbidity. Although it is well known that not all the exposed individuals develop these conditions, the mechanisms leading to a vulnerable or a resilient phenotype for mood and metabolic disorders, as consequences of ELS exposure, are still not fully understood. In this study, we used a prenatal stress (PNS) model, mimicking perinatal adversities, to investigate the impact of ELS on metabolic function, stress-related and inflammatory markers in adult male and female offspring, with a particular focus on vulnerable or resilient phenotypes. PNS exposure was associated with a dysregulation of stress-related and metabolic markers both in the liver and also in the ventral hippocampus, with vulnerable males exhibiting increased insulin receptor levels and dysregulated expression of adipokine receptors (such as leptin and adiponectin). In contrast, female animals did not exhibit these changes. Additionally, PNS induced a pronounced neuroinflammatory response in the ventral hippocampus of vulnerable male rats, characterized by an upregulation of microglial activation markers. Interestingly, a similar pro-inflammatory status was observed in the liver of PNS-exposed males regardless of the pathologic phenotype; however, anti-inflammatory markers were upregulated only in resilient animals, suggesting an active mechanism of resilience. These findings suggest that specific metabolic and inflammatory changes underlie, with a sex-specific effect, the onset of a vulnerable phenotype to PNS and highlight the importance of targeting these pathways in the treatment of mood disorders and metabolic comorbidities.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease afflict millions of individuals globally and are significant sources of disease mortality. While the molecular mechanisms underlying such diseases are unclear, environmental and social factors, such as cigarette smoke and obesity, increase the risk of disease development. Yet, not all smokers or obese individuals will develop chronic respiratory diseases. The mitogen-activated protein kinase p38α is abnormally active in such maladies, but its contribution, if any, to disease etiology is unknown. To assess whether p38α activation per se in the lung could impose disease symptoms, we generated a transgenic mouse model allowing controllable expression of an intrinsically active variant, p38αD176A+F327S, specifically in lung alveolar type 2 pneumocytes. Sustained expression of p38αD176A+F327S did not appear to induce obvious pathological outcomes or to exacerbate inflammatory outcomes in mice challenged with common respiratory disease triggers. However, mice expressing p38αD176A+F327S in alveolar type 2 cells and fed with a high-fat diet exhibited increased numbers of airway eosinophils and lymphocytes, upregulated levels of proinflammatory cytokines and chemokines including interleukin-1β and eotaxin, as well as a reduction in levels of leptin and adiponectin within the lung. Neither high-fat diet nor p38αD176A+F327S alone induced such outcomes. Perhaps in obese individuals with associated respiratory diseases, elevated p38α activity which happens to occur is the factor that promotes their development.

Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin's practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity, and gestational diabetes. It has been noted that when leptin has impaired signaling in CNS, causing the lack of its normal function in energy balance, it results in leptin resistance, leading to a rise in its concentration in peripheral tissues. Our research paper will shed highlighting on potentially targeting the leptin receptor and its cellular signaling in suppressing breast cancer progression.

Clozapine, the preferred medication for treatment-resistant schizophrenia, elevates leptin and pro-inflammatory cytokine levels in patients' blood. Inhibition of the clozapine metabolic enzyme CYP1A2 can potentially lead to toxicity and pneumonia. Leptin has a pro-inflammatory effect on the immune system. This study explores whether polymorphisms in the leptin (LEP) and leptin receptor (LEPR) genes are associated with increased risk of clozapine-induced pneumonia.

A retrospective cohort study was conducted with 302 consecutive schizophrenia patients who had been on clozapine for at least 6 months. Blood samples were collected to identify genetic polymorphisms in the LEP and LEPR genes, and the association between these polymorphisms and pneumonia incidence was analyzed using Cox proportional hazards models.

Among the SNPs in the LEPR gene, individuals with the A/A genotype of rs1137101 had a 14.96-fold higher pneumonia risk than those with the G/G genotype (p = 0.001). Carriers of the G/G genotype of rs1805096 had a 3.72-fold increased risk compared to those with A/A (p = 0.033). For rs6657868, the A/G and G/G genotypes were associated with 2.23-fold (p = 0.005) and 6.73-fold (p = 0.013) higher risks, respectively, compared to the A/A genotype. Similarly, for rs9436746, the A/C and C/C genotypes had 2.25-fold (p = 0.005) and 5.37-fold (p = 0.029) increased risks, respectively, compared to A/A.

LEPR polymorphisms associated with an increased risk of pneumonia in Taiwanese schizophrenia patients treated with clozapine.

Leptin plays a dual role in heart failure (HF), acting as either a primary driver or a secondary phenomenon depending on the HF subtype. In HF with preserved ejection fraction (HFpEF), chronic hyperleptinemia is a primary mediator of disease initiation and progression, closely linked to obesity and metabolic dysfunction. Elevated leptin levels promote systemic inflammation, sympathetic nervous system activation, arterial stiffness, myocardial hypertrophy, fibrosis, and sodium retention, culminating in diastolic dysfunction and elevated ventricular filling pressures. Conversely, in HF with reduced ejection fraction (HFrEF), elevated leptin levels arise as a secondary response to myocardial dysfunction, systemic inflammation, and tissue hypoperfusion. Here, leptin exacerbates cardiac dysfunction by amplifying neurohormonal activation, inflammation, and cardiac remodeling. Understanding these distinct roles has potential therapeutic implications. In HFpEF, interventions such as weight loss, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists can improve symptoms and prognosis, partly by mitigating chronic hyperleptinemia. Furthermore, leptin-specific therapies should be investigated in clinical trials as potential approach in managing cardiometabolic HFpEF. In HFrEF, management focuses on guideline-directed therapies targeting neurohormonal activation-the key mechanism driving disease progression. However, future research should explore whether modulating leptin signaling could provide additional benefits translated in hard clinical endpoints. By framing leptin as the initiator ("chicken") in HFpEF and a consequence ("egg") in HFrEF, this manuscript highlights the need for individualized, integrated treatment strategies. Addressing both metabolic and cardiovascular components could potentially further improve patient outcomes and quality of life.

Inner retinal thinning precedes clinical evidence of retinopathy in prediabetes and diabetes mellitus (DM), and may contribute to retinopathy development and progression. Serum levels of the adipokines leptin and adiponectin are inversely related in the setting of impaired glucose homeostasis, but their potential association with inner retinal thickness is unknown. In this prospective study, both eyes from 24 individuals with prediabetes or type 2 DM (glycated hemoglobin [HbA1c] ≥ 5.7) and 16 controls (HbA1c < 5.7) underwent spectral-domain optical coherence tomography imaging of the macula, and thickness of the nerve fiber layer (NFL) and ganglion cell layer-inner plexiform layer (GCL-IPL) was analyzed in each subfield of the Early Treatment Diabetic Retinopathy Study grid. Serum samples were collected and metabolic factors, including adiponectin and leptin, were measured. Adjusted regression analyses revealed inverse associations of these adipokines with NFL thickness that did not differ between prediabetes/DM and controls, but differential positive associations of adiponectin with GCL-IPL thickness only in the prediabetes/DM group. The results of our pilot study suggest opposing roles for adiponectin and leptin in the retina, similar to their relationship in systemic disease, and suggest that serum adiponectin may represent a potential clinical biomarker for inner retinal thickness in patients with elevated HbA1c.

Frozen shoulder (FS) is a complex and multifactorial condition characterized by persistent inflammation, fibrosis, and metabolic dysregulation. Despite extensive research, the underlying drivers of FS remain poorly understood. Recent findings indicate the coexistence of pro-inflammatory and fibrosis-resolving macrophages within affected tissues, suggesting a dysregulated immune response influenced by metabolic and neuroendocrine factors. This review proposes that leptin resistance, a hallmark of metabolic syndrome and chronic inflammation, may play a central role in FS pathogenesis by impairing macrophage polarization, perpetuating inflammation, and disrupting fibrosis resolution. The JAK-STAT signaling pathway, critically modulated by leptin resistance, may further contribute to immune dysregulation by sustaining inflammatory macrophage activation and interfering with tissue remodeling. Additionally, FS shares pathogenic features with fibrotic diseases driven by TGF-β signaling, mitochondrial dysfunction, and circadian disruption, further linking systemic metabolic dysfunction to localized fibrotic pathology. Beyond immune and metabolic regulation, alterations in gut microbiota, bacterial translocation, and chronic psychosocial stress may further exacerbate systemic inflammation and neuroendocrine imbalances, intensifying JAK-STAT dysregulation and leptin resistance. By examining the intricate interplay between metabolism, immune function, and fibrotic remodeling, this review highlights targeting leptin sensitivity, JAK-STAT modulation, and mitochondrial restoration as novel therapeutic strategies for FS treatment. Future research should explore these interconnections to develop integrative interventions that address both the metabolic and immune dysregulation underlying FS, ultimately improving clinical outcomes.

Impacts of milk proteins (MPs) on inflammation are uncertain. The current systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the effects of whey protein (WP), casein protein (CP), or MP supplementation on serum levels of cytokines and adipokines in adults.

A comprehensive search of various online databases was conducted to find appropriate clinical trials published until September 2024. A random-effect statistical model was implemented.

The meta-analysis included 53 RCTs. It was indicated that MP supplements had no substantial effects on serum values of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), adiponectin, and leptin. However, there were statistically significant decreases in serum levels of interleukin-6 (IL-6) following supplementation with MP (weighted mean difference (WMD): - 0.25 pg/mL, 95% CI - 0.48, - 0.03; P = 0.026) in the intervention group compared with the control group.

This study revealed that MP supplementation may not have any considerable impacts on the levels of cytokines and adipokines.

Prostate cancer (PCa) is known as the second most common cancer and has one of the highest incidences among male cancers in the United States. In addition, obesity and metabolic syndrome are a rising and continuous issue in the United States, with 41.9% of individuals as obese. The importance of highlighting these figures is the possibility of PCa having a progressive relationship with obesity and metabolic syndromes. The drugs developed for treating obesity and diabetes pose an exciting possibility of therapeutic application for cancer in efforts to relieve the population's rising numbers. Although this connection has not been established in detail, there are some PCa key biomarkers, and their interactions with metabolic products found in obese, diabetic, and PCa patients can provide good starting points for further investigation. One of the significant links between PCa, obesity, and metabolic disease may be due to insulin metabolism. A downstream target identified that could be the link between PCa, metabolic syndromes, and obesity is the forkhead box C2 (FOXC2). FOXC2 has been known to inhibit some insulin-resistant genes and cause the proliferation of PCa. The relationships of FOXC2, insulin resistance, and GLP-1 receptor agonists as potential therapeutic applications have not been thoroughly explored. This review covers a broad relationship of PCa, obesity, metabolic syndromes, possible drugs, and therapeutic targets.

The prevalence of noncommunicable inflammatory disease is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapeutic strategies are needed to effectively deal with this issue. One promising approach is leveraging microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory, immunoregulatory, and stress-resilience properties. This study aimed to assess whether weekly subcutaneous administrations of a whole-cell, heat-killed preparation of M. vaccae ATCC 15483 (eleven injections initiated one week before the onset of the diet intervention), relative to vehicle injections, in adolescent male C57BL/6N mice can mitigate inflammation associated with Western-style diet-induced obesity, which is considered a risk factor for a number of metabolic and inflammatory diseases. Our results show that treatment with M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations. The Western-style diet, relative to a control diet condition, decreased alpha diversity and altered the community composition of the gut microbiome, increasing the Bacillota to Bacteroidota ratio (formerly referred to as the Firmicutes to Bacteroidetes ratio). Despite the finding that M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations, it had no effect on the diversity or community composition of the gut microbiome, suggesting that it acts downstream of the gut microbiome to alter immunometabolic signaling. M. vaccae ATCC 15483 reduced baseline levels of biomarkers of hippocampal neuroinflammation and microglial priming, such as Nfkbia and Nlrp3, and notably decreased anxiety-like defensive behavioral responses. The current findings provide compelling evidence supporting the potential for M. vaccae ATCC 15483 as a promising intervention for prevention or treatment of adverse immunometabolic outcomes linked to the consumption of a Western-style diet and the associated dysbiosis of the gut microbiome.

Obesity, a pandemic health problem, is now considered as a chronic inflammatory state, related to many autoimmune diseases, such as multiple sclerosis. Thus, adipokines, inflammatory mediators secreted by adipose tissue, play an important role modulating the immune response. In this context, obesity, especially during adolescent age, seems to be a key factor for the development of multiple sclerosis. Leptin, the main pro-inflammatory adipokine secreted by the adipose tissue, has been found increased in patients with multiple sclerosis and is able to regulate the immune system promoting a pro-inflammatory response. Leptin signaling in both innate and adaptative immune cells might have immunomodulatory effects in the context of multiple sclerosis. In this way, leptin has been found to produce a Th1 and Th17 response, increasing M1 macrophages and decreasing regulatory T cells and Th2 response. Moreover, circulating inflammatory adipokines, such as leptin, have been found in people with multiple sclerosis. In the present work, we are reviewing literature to update the body of knowledge regarding the role of obesity and leptin in multiple sclerosis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage, and bone destruction. Several studies have shown that leptin plays an important role in the pathophysiology of RA disease. This study aimed to evaluate serum levels of leptin in RA patients receiving biologic drugs compared to RA patients managed by non-biologic drugs, and healthy individuals.

In this case-control study, three groups including RA patients receiving biological drugs (remission RA patients; n = 20), RA patients receiving DMARDs (active RA patients; n = 20), and healthy controls (n = 20) were included. Serum leptin levels and inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were measured in all participants. These measurements were subsequently compared across the three groups. Also, the correlation between leptin and inflammatory markers in each group was evaluated.

In this study serum leptin levels in remission RA patients, active RA patients, and healthy individuals were 14.49 ± 6.73, 16.94 ± 7.72, and 7.59 ± 5.94, respectively. Serum leptin level was significantly higher in patients with RA compared to healthy controls. No significant difference was observed in serum leptin levels between the two groups of RA patients (P < 0.001). There was a lost correlation between leptin and inflammatory markers in patients with active RA. However, a new correlation between leptin and inflammatory markers emerged in RA patients receiving biological drugs.

Our findings suggest that anti-TNF-alpha agents do not modulate serum leptin levels in RA patients. However, these agents may change a correlation between leptin and C-reactive protein (CRP) that is absent in patients with active RA.

Not applicable in case control study.

Background/Objectives: Lipedema is a progressive disease that results in the bilateral and symmetrical accumulation of subcutaneous fat in the legs and/or arms, affecting almost exclusively women. Methods: A comprehensive review of the peer-reviewed literature was conducted between November 2024 and February 2025. Results: The pathophysiology of lipedema is complex and, especially in the early stages, shows similarities to obesity, involving adipocytes, adipose tissue-resident macrophages, and endothelial cells. In lipedema, systemic levels and the adipocyte expression of the classical adipokines adiponectin and leptin appear normal, while it remains unclear if markers of inflammation and oxidative stress are increased. Macrophages in the adipose tissue of patients have an anti-inflammatory M2 phenotype and express high levels of the scavenger receptor CD163. These cells affect adipogenesis and seem to have a central role in adipose tissue accumulation. Increased lymphatic and blood vessel permeability are comorbidities of lipedema that occur in early disease states and may contribute to disease progression. Conclusions: This review summarizes our current understanding of the pathophysiology of lipedema with a focus on the role of stromal vascular localized M2 macrophages.

Obesity is a chronic inflammatory disease that affects more than 1 billion people worldwide and is associated with various metabolic and physiological dysfunctions, directly impacting the dynamics of the immune response, partly due to elevated leptin levels. Leptin is an important peptide hormone that regulates neuroendocrine function and energy homeostasis, with its blood levels reflecting energy reserves, fat mass, or energy deprivation. This hormone also plays a fundamental role in regulating immune function, including the activity of NK cells, which are essential components in antiviral and antitumor activity. In obese individuals, leptin resistance is commonly established, however, NK cells and other immune components remain responsive to this hormone. So far, leptin has demonstrated paradoxical activities of these cells, often associated with a dysfunctional profile when associated with obesity. The excessive fat is usually related to metabolic remodeling in NK cells, resulting in compromised antitumor responses due to reduced cytotoxic capacity and decreased expression of cytokines important for these defense mechanisms, such as IFN-γ. Therefore, this review approaches a better understanding of the immunoendocrine interactions between leptin and NK cells in the context of obesity.

Adverse childhood experiences (ACEs) are associated with a greater risk of obesity and cardiometabolic disease. Adipokines, including leptin and adiponectin, play vital roles in biological processes linked to obesity and cardiometabolic risk. The adiponectin/leptin ratio may represent a marker of impaired hormonal regulation of adipose tissue. Prior cross-sectional studies suggest patterns of higher plasma leptin and lower adiponectin among adults who have experienced ACEs. This study addresses whether ACEs influence longitudinal changes in leptin, adiponectin, and the adiponectin/leptin ratio, after accounting for current chronic stress and adiposity.

This longitudinal study included 192 middle-aged mothers (mean age = 46.78 years) experiencing higher (n = 108) and lower (n = 84) chronic caregiving stress. Adipokines and adiposity were measured at three timepoints: T1 (baseline), T2 (15 months later), and T3 (30 months after T1). ACEs were assessed retrospectively using the Childhood Trauma Questionnaire.

Mixed-effect models showed that leptin and adiponectin increased over time. Greater ACEs exposure was associated with larger increases in leptin over time, but it was not related to adiponectin or the adiponectin/leptin ratio. Current caregiving stress was not related to leptin and adiponectin levels and did not interact with ACEs in predicting adipokine levels. Mediation analyses revealed that increases in waist circumference partially mediated the association between ACEs and increases in leptin over time.

ACEs may increase vulnerability to cardiometabolic risk in midlife caregiving mothers through its influence on longitudinal changes in leptin and central adiposity.

The comparison of thyroid profile and serum leptin levels among patients with metabolic syndrome who did not have hypothyroidism is of interest. Hence, we recruited 40 healthy controls and 80 patients with metabolic syndrome where 40 patients had hypothyroidism and 40 patients are without hypothyroidism. Blood sugar levels, thyroid profiles, lipid profiles and serum leptin levels were measured and compared between the metabolic syndrome and control groups. The serum leptin levels of patients with hypothyroidism were considerably higher (P=0.0001**) when compared to metabolic syndrome patients without hypothyroidism and controls. Furthermore, there was a substantial positive correlation between leptin levels and thyroid stimulating hormone (TSH). Results show that serum leptin and TSH are significantly correlated among metabolic syndrome patients with and without hypothyroidism. Thus, monitoring of leptin levels among metabolic syndrome patients with and without hypothyroidism is relevant.

Gait stability prevents falls and injuries during physical activities. Muscle strength, aging, and co-existing chronic diseases are factors that affect gait stability. Leptin is an adipokine with pro-inflammatory properties. Several reports demonstrated an association between serum leptin and a reduction in muscle strength. Given the above relationships, we hypothesized that serum leptin could be associated with gait stability. To test this, 146 apparently healthy university students were recruited. Data collection involved anthropometric measurements, physical activity (PA) data, gait parameters, and serum leptin levels. A gait instability index was derived from the percentages of double support time and walking asymmetry (WA) collected from smartphones. Females demonstrated higher leptin levels and WA despite a lower body mass index (BMI). Lower PA levels were also observed among females. Leptin levels were negatively correlated with WA, step count, and vigorous PA (p < 0.05). These correlations remained significant following correction for leptin by BMI. Using logistic regression, a higher leptin-to-BMI ratio was associated with high gait instability (OR = 9.97, 95%CI: 4.17-23.84, p < 0.001). After stratification by sex, this association was only evident among females (OR = 6.09, 95%CI: 1.04-35.56, p = 0.045). These findings suggest a sex-based association between serum leptin and gait stability among apparently healthy students.

Obesity, the fifth leading cause of death globally and linked to chronic low-grade inflammation and development of numerous severe pathologies, is a major public health problem. Fermented foods, probiotics, and postbiotics emerge as promising avenues for combating obesity and inflammation. The aim of our study was to develop and characterize phyto-postbiotics corresponding to prebiotic compounds fermented by gut bacteria, which could act on obesity and related-inflammation. Chicory extract fermented by Akkermansia muciniphila (C-Akm) was selected as the most antioxidant of 20 fermented extracts. The identification of metabolites derived from C-Akm extract has enabled us to detect mostly amino acids, acids, and some polyphenols (daidzein and genistein). The anti-inflammatory and anti-obesity activities of C-Akm extract were studied by testing the extract (50 μg/mL) on the polarization of THP-1 into macrophages, the secretion of pro-inflammatory cytokines in LPS-stimulated PBMCs, and the secretion of leptin and adiponectin in adipospheroids derived from human adipose stem cells. Finally, the extract was examined in 3D co-culture model mimicking inflamed obese adipose tissue. We found that C-Akm extract decreased ROS generation, TNF-α and Il-6 gene expression in polarized macrophages, INFγ and IL-17A secretion in LPS-stimulated PBMCs stimulated with LPS. It also decreased leptin expression while increasing adiponectin and HSL expression levels in both adipocytes and co-cultures. In addition, C-Akm extract stimulated adiponectin secretion in the co-culture model. Finally, our in vitro investigations demonstrated the potential benefits of C-Akm extract in the prevention and treatment of obesity-related inflammation.

Obesity has become a significant public health concern, strongly linked to various diseases, particularly gynecologic and breast cancers. This bibliometric review aims to analyze global research trends on overweight women, particularly those with gynecologic and breast cancers, to identify research hotspots, key contributors, and emerging areas of study.

A comprehensive bibliometric analysis was conducted using the Web of Science Core Collection (WoSCC) database, covering the period from January 2013 to September 2024. Articles were screened and analyzed using tools such as VOSviewer and Biblioshiny platform, with metrics including publication volume, citation analysis, and co-authorship networks. Key areas of focus were global research trends, leading countries, institutions, authors, journals, and keyword analysis.

A total of 1452 publications were analyzed. Research activity on the association between obesity and gynecologic/breast cancer has steadily increased, with the United States leading in publications and citations, followed by China and Italy. Core journals included Breast Cancer Research and Treatment and Gynecologic Oncology. Key research areas identified through keyword analysis include the relationship between body mass index (BMI) and cancer risk, survival rates in cancer patients, physical activity, and the role of adipose tissue inflammation in tumor progression. Emerging topics include extracellular vesicles and cancer-associated fibroblasts.

Global research on the relationship between obesity and female-specific cancers has shown significant growth. The findings highlight BMI, survival, and physical activity as central themes. Future research should explore the molecular mechanisms linking obesity to cancer and evaluate weight loss interventions for cancer prevention and treatment.

Introduction: Chronic rhinosinusitis (CRS) and asthma frequently coexhist in children leading to the unified airway theory. Although obesity has been associated with CRS and asthma in adults, studies exploring that association in children are limited. The goal of this study was to evaluate the association between obesity and the unified airway in children. Methods: A retrospective case-control study was performed in children aged 2 to 18 years presenting to our clinic between July 2020 and February 2024. Patient's demographics and comorbidities were reviewed. Children's obesity was classified based on their percentile body mass index of 95% and more. Asthma and CRS diagnoses were determined based on published guidelines. Results: A total of 406 pediatric patients met criteria, with 130 children (32%) with obesity. Children with CRS had a mean computed tomography (CT) Lund-Mackay score of 7.2 (SD of 6.3) and a mean endoscopy modified Lund-Kennedy score of 2.7 (SD of 2.9). Children with obesity were older (11.3 years vs 10.2 years, P = .039) and more likely to have asthma (28.5% vs 15.2%, P = .002) and obstructive sleep apnea (26.2% vs 13%, P = .001). Multivariate logistic regression showed an association between obesity and asthma (OR = 1.84, P = .029), but not with CRS (OR = 1.08, P = .856) or allergic rhinitis (OR = 1.05, P = .856). Conclusion: This study suggests an association between obesity and asthma but not with CRS in children. Further studies should explore whether there is any role for obesity in the treatment of CRS.

Uterine physiology encompasses the intricate processes governing the structure, function, and regulation of the uterus, a pivotal organ within the female reproductive system. The escalating prevalence of obesity has emerged as a significant global health issue, profoundly impacting various facets of well-being, including female reproductive health. These effects extend to uterine structure and function, influencing reproductive health outcomes in women. They encompass alterations in uterine morphology, disruptions in hormonal signaling, and inflammatory processes. Insulin and leptin, pivotal hormones regulating metabolism, energy balance, and reproductive function, play crucial roles in this context. Insulin chiefly governs glucose metabolism and storage, while leptin regulates appetite and energy expenditure. However, in obesity, resistance to both insulin and leptin can develop, impacting uterine function. Inflammation and oxidative stress further exacerbate the development of uterine dysfunction in obesity. Chronic low-grade inflammation and heightened oxidative stress, characteristic of obesity, contribute to metabolic disruptions and tissue damage, including within the uterus. Obesity significantly disrupts menstrual cycles, fertility, and pregnancy outcomes in women. The accumulation of excess adipose tissue disrupts hormonal equilibrium, disturbs ovarian function, and fosters metabolic irregularities, all of which detrimentally impact reproductive health.

Background and objective There is growing concern regarding metabolic and inflammatory disorders globally, underscoring the need for effective nonpharmacological interventions. Irisin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leptin are biomarkers of metabolic and inflammatory health. In this study, we aimed to investigate the comparative effects of basil seed supplementation or endurance exercise on biomarkers of chronic oxidative stress. Methods This prospective observational study enrolled 60 participants who were randomly divided into two groups: Group A (basil seeds, n=30) and Group B (endurance exercise, n=30). Participants in Group A consumed 10 grams of soaked basil seeds daily for eight weeks, while those in Group B underwent a supervised endurance exercise regimen (45 minutes/day, five days/week). Biomarkers, including irisin, IL-6, TNF-α, and leptin, were quantified using enzyme-linked immunosorbent assay (ELISA) both at baseline and post-intervention. Within-group and between-group differences were analyzed using paired and independent t-tests, with a significance threshold of p<0.05. Results Overall, the baseline characteristics in Group A (age: 35.4 ± 5.0 years; BMI: 24.5 ± 2.3 kg/m²) and B (age: 34.9 ± 4.8 years; BMI: 24.9 ± 2.4 kg/m²) were comparable (p>0.05). Significant changes were observed in both groups post-intervention. Irisin levels increased moderately in group A (47.23 ± 4.8 µg/mL to 50.79 ± 5.13 µg/mL, p<0.01), and IL-6, TNF-α, and leptin decreased (IL-6: 28.2 ± 2.13 pg/mL to 18.1 ± 2.01 pg/mL, p<0.01; TNF-α: 34.5 ± 2.72 pg/mL to 23.6 ± 2.64 pg/mL, p<0.01; and leptin: 8.4 ± 1.96 ng/mL to 3.9 ± 0.83 ng/mL, p<0.01). Group B showed a significant increase in irisin (44.04 ± 3.58 µg/mL to 150.1 ± 9.32 µg/mL, p<0.001) and a non-significant rise in IL-6 (31.65 ± 2.4 pg/mL to 35.64 ± 3.17 pg/mL, p>0.05). TNF-α levels increased in Group B (31.65 ± 3.27 pg/mL vs. 61.66 ± 3.85 pg/mL, p<0.001) and decreased in Group A, while leptin levels slightly decreased in Group B (7.94 ± 1.27 ng/mL vs. 4.19 ± 0.64 ng/mL, p>0.05). Conclusions Supplementation with basil seed and exercise training with endurance exercise had distinct effects on biomarkers of metabolism and inflammation. Irisin levels were significantly improved by endurance exercise, while basil seeds were most effective in reducing IL-6, TNF-α, and leptin. The findings suggest that basil seeds and exercise provide synergistic effects against metabolic and inflammatory diseases.

Pentadecanoic acid (C15:0, PDA) is an odd and minor fatty acid that has been neglected in the literature until the last decade. Indeed, as a specific fatty acid of dairy fat, PDA was only used as a biomarker of dairy fat consumption. Lately, PDA was first correlated negatively with the incidence of metabolic syndrome disorder, then its physiological effects have been investigated as a protective fatty acid. PDA supplementation has been demonstrated as negatively correlated with elevated levels of leptin, plasminogen activator inhibitor-1 and insulin, and has been shown to exhibit sensitizing insulin effects with activation of AMPK pathway. PDA also reduced the severity of metabolic dysfunction-associated steatohepatitis (MASH), notably through reduced alanine transaminase and pro-inflammatory cytokines levels. The final effect described for PDA is its ability to display anti-inflammatory properties in several pathology models. Hence, considering these multiple effects, the presence of PDA could be associated with a healthier physiological state, this raises the question of whether the presence of PDA in the body, in adequate quantities, is needed to participate to health maintenance. PDA is not synthesized in sufficient quantities endogenously, so it must be provided by the diet, mainly through dairy fat, although other types of food can also contribute to the dietary intake of PDA. Essential fatty acids are described as not being endogenously synthesized in sufficient and required quantities to maintain physiological health. Thus, PDA might gather both conditions to be described as essential, yet further investigations on both criteria are needed to enhance knowledge on this odd chain fatty acid with promising impact as potential protective supplement nutrient.

Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is largely driven by obesity-related factors, including adipokines and bioactive peptides primarily secreted by the adipose tissue, such as leptin, adiponectin, and resistin. These molecules link metabolic dysregulation to cardiovascular dysfunction, influencing HFpEF progression and patient outcomes Methods: A comprehensive literature search was conducted in PubMed up to 20 November 2024, using keywords and MeSH terms, such as "HFpEF", "adipokines", "leptin", "adiponectin", and "resistin", yielding 723 results. Boolean operators refined the search, and reference lists of key studies were reviewed. After screening for duplicates and irrelevant studies, 103 articles were included, providing data on adipokines' roles in HFpEF pathophysiology, biomarkers, and therapeutic implications.

Both preclinical and clinical studies have demonstrated that adipokines play a role in modulating cardiovascular function, thereby contributing to the development of cardiometabolic HFpEF. Leptin promotes myocardial hypertrophy, fibrosis, endothelial dysfunction, and inflammation, though contradictory evidence suggests potential cardioprotective roles in subgroups like obese African American women. Adiponectin generally offers protective effects but presents a paradox, where elevated levels may correlate with worse outcomes, which may reflect either a compensatory response to cardiac dysfunction or a maladaptive state characterized by adiponectin resistance. Resistin is associated with increased cardiovascular risk through pro-inflammatory and pro-fibrotic effects, though its role in HFpEF requires further clarification. Other adipokines, like retinol-binding protein 4 and omentin-1, have emerged as potential contributors. Despite growing insights, clinical translation remains limited, underscoring a significant gap between experimental evidence and therapeutic application.

Future research should focus on targeted interventions that modulate adipokine pathways to potentially improve HFpEF outcomes. Innovative treatment strategies addressing underlying metabolic disturbances and adipokine dysregulation are essential for advancing the management of this challenging condition.

Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.

Leptin is not only the main regulator of energy balance, but also it affects the reproductive and immune systems. Leptin and its receptors are expressed in the endometrium and are actively involved in the embryo implantation. According to numerous studies, expression and level changes of leptin are associated with the inflammatory and autoimmune diseases, including endometriosis and chronic endometritis. Hyperplastic and inflammatory diseases of the uterus are accompanied by a violation of the receptivity of the endometrium due to the dysregulation of many factors involved in proliferation, vascularization and decidualization of cells. Activity of most of these factors is due to the leptin action, however, there are no studies of the direct effect of leptin in the pathogenesis of disorders of the endometrium in hyperplastic and inflammatory diseases.Thus, the purpose of this literature review was to describe the putative molecular mechanisms of the effect of leptin on the development of endometrial pathology.Literature search was carried out from 03/20/2023 to 05/11/2023 using scientific literature databases: NCBI PubMed, Google Scholar (foreign sources), Cyberleninka, Elibrary (domestic sources): references for the period 1995-2023 were analyzed. The following keywords were used for the search: leptin, endometrial dysfunction, endometrial receptivity, inflammation, pelvic inflammatory disease.

Childhood obesity represents a significant public health concern, imposing a substantial burden on the healthcare system. Furthermore, weight-loss programs often exhibit reduced effectiveness in adults who have a history of childhood obesity. Therefore, early intervention against childhood obesity is imperative. Presently, the primary method for diagnosing childhood obesity relies on body mass index (BMI), yet this approach has inherent limitations. Leptin, a satiety hormone produced by adipocytes, holds promise as a superior tool for predicting both childhood and subsequent adulthood obesity. In this review, we elucidate the tools employed for assessing obesity in children, delve into the biological functions of leptin, and examine the factors governing its expression. Additionally, we discuss maternal and infantile leptin levels as predictors of childhood obesity. By exploring the relationship between leptin levels and weight loss, we present leptin as a potential indicator of the effectiveness of obesity interventions.

Exploring new inhibitors with good bioavailability and high selectivity for managing type 2 diabetes mellitus (T2DM) and its associated complications is a major challenge for research, academia, and the pharmaceutical industry. Protein tyrosine phosphatase-1B (PTP1B) arose as an important negative regulator in insulin signaling pathways associated with metabolic disorders, including T2DM and obesity. Novel neutral compounds with a benzene-sulfonamide scaffold were designed and synthesized based on structural- and ligand-based drug design strategies for fragment growth. Promising hits against PTP1B were identified through in vitro enzymology inhibition assay. Mechanistic aspects of the compound's different inhibition activities were rigorously investigated through molecular docking coupled with explicit dynamics simulations. Four identified hits, 3c, 8, 10a, and 11, with sub-micromolar PTP-1B IC50 and significant predicted pharmacokinetic and pharmacodynamic parameters, were further biologically evaluated for their anti-diabetic, anti-obesity, anti-inflammatory, and anti-oxidant effects in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2DM rat model. All these hit compounds exhibited a significant anti-diabetic and anti-obesity effect and a significant efficacy in reducing oxidative stress and increasing anti-oxidant enzymes while reducing inflammatory markers. Improving compound potency was further highlighted by improving the pharmacokinetic profile of the most active compound, 10a, through nano formulation. Compound 10a nano formulation showed the most promising anti-diabetic and anti-obesity effects and a remarkable histopathological improvement in all organs studied.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic β-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

The effects of exercise training combined with plant-based diets (PBD) on leptin and adiponectin levels have been studied. However, little is known regarding the impact of exercise training combined with PBD on leptin and adiponectin levels in adults with or without chronic diseases.

PubMed, Web of Science, and Scopus were searched to identify original articles, published until May 2024, to assess the effects of exercise training combined with PBD on leptin and adiponectin levels in adults with or without chronic diseases. Standardized mean differences (SMD) and 95% confidence intervals were calculated using random models.

Nine studies comprising 960 participants with overweight and obesity were included in the current meta-analysis. Exercise training combined with PBD reduced leptin [SMD = -0.33 (95% CI: -0.62 to -0.04); p = 0.025] while increasing adiponectin [SMD = 0.93 (95% CI: 0.12 to 1.74); p = 0.024] levels.

Exercise training combined with PBD is suggested as a non-invasive intervention for reducing leptin while increasing adiponectin levels to control body mass and other disorders related to obesity in adults.

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being.

Leptin is known for its metabolic, immunomodulatory and neuroendocrine properties, but the full spectrum of molecules downstream of leptin and relevant underlying mechanisms remain to be fully clarified. Our objective was to identify proteins and pathways influenced by leptin through untargeted proteomics in two clinical trials involving leptin administration in lean individuals.

We performed untargeted liquid chromatography-tandem mass spectrometry serum proteomics across two studies a) Short-term randomized controlled crossover study of lean male and female humans undergoing a 72-h fast with concurrent administration of either placebo or high-dose leptin; b) Long-term (36-week) randomized controlled trial of leptin replacement therapy in human females with acquired relative energy deficiency and hypoleptinemia. We explored longitudinal proteomic changes and run adjusted mixed models followed by post-hoc tests. We further attempted to identify ontological pathways modulated during each experimental condition and/or comparison, through integrated qualitative pathway and enrichment analyses. We also explored dynamic longitudinal relationships between the circulating proteome with clinical and hormonal outcomes.

289 and 357 unique proteins were identified per each respective study. Short-term leptin administration during fasting markedly upregulated several proinflammatory molecules, notably C-reactive protein (CRP) and cluster of differentiation (CD) 14, and downregulated lecithin cholesterol acyltransferase and several immunoglobulin variable chains, in contrast with placebo, which produced minimal changes. Quantitative pathway enrichment further indicated an upregulation of the acute phase response and downregulation of immunoglobulin- and B cell-mediated immunity by leptin. These changes were independent of participants' biological sex. In the long term study, leptin likewise robustly and persistently upregulated proteins of the acute phase response, and downregulated immunoglobulin-mediated immunity. Leptin also significantly and differentially affected a wide array of proteins related to immune function, defense response, coagulation, and inflammation compared with placebo. These changes were more notable at the 24-week visit, coinciding with the highest measured levels of serum leptin. We further identified distinct co-regulated clusters of proteins and clinical features during leptin administration indicating robust longitudinal correlations between the regulation of immunoglobulins, immune-related molecules, serpins (including cortisol and thyroxine-binding globulins), lipid transport molecules and growth factors, in contrast with placebo, which did not produce similar associations.

These high-throughput longitudinal results provide unique functional insights into leptin physiology, and pave the way for affinity-based proteomic analyses measuring several thousands of molecules, that will confirm these data and may fully delineate underlying mechanisms.

Obesity increases reactive oxygen species production and alters adipokines levels, resulting in a low-grade chronic inflammation state, which contributes to tissue metabolic dysfunction. 10-gingerol, a phenol present in ginger, has shown potential anti-obesogenic effects in vitro. However, the antioxidant and anti-inflammatory properties of 10-gingerol have not been approached. The aim of this study was to investigate the effects of 10-gingerol on antioxidant enzymes' expression and adipokine production in 3T3-L1 adipocytes in response to lipopolysaccharide (LPS)-induced inflammation.

10-gingerol antioxidant capacity was assessed through Oxygen Radical Absorbance Capacity (ORAC) , Ferric Reducing Antioxidant Power (FRAP), and radical scavenging activity of 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays. 3T3-L1 cells were differentiated and stimulated with 100 ng/mL LPSs. Then, 15 µg/mL 10-gingerol was added for 48 h. The mRNA expression and protein abundance of antioxidant enzymes were evaluated by qPCR and Western blot, respectively. Adipokine levels were determined by ELISA.

10-gingerol showed low FRAP and DPPH values but a moderate ORAC value. Moreover, 10-gingerol increased Gpx1 and Sod1 but downregulated Cat expression. Additionally, 10-gingerol significantly increased CAT and GPx1 levels but not SOD-1. Finally, adiponectin and leptin concentrations were increased while resistin and tumor necrosis factor alpha (TNFα) were decreased by 10-gingerol.

10-gingerol presented antioxidant potential by increasing antioxidant enzymes and attenuated LPS-induced inflammation by modulating adipokines in 3T3-L1 adipocytes.

Severe obesity results in high cardiovascular risk (CVR), increasing morbidity, and mortality. New and improved methods are needed to detect cardiovascular diseases rapidly in severe obesity. microRNAs (miRNAs) has shown promise as diagnostic tools. This study aimed to identify plasma miRNAs useful as biomarkers of CVR in people with severe obesity.

The study included 66 people with severe obesity classified in groups with atheroma (n = 32) and free of plaques (n = 34). Plasma samples were collected 1 month before bariatric surgery and at 6 and 12 months of follow-up. Participants were screened for the levels of 188 miRNAs, and 24 promising candidates were individually validated by quantitative polymerase chain reaction.

After validation, 5 of the 24 miRNAs showed significant differences over time in both groups: miR-375 increased after bariatric surgery, whereas miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p exhibited decreased expression after bariatric surgery. The expression of 3 of the 24 miRNAs also differed between patients with and without atheroma: subjects with plaque had lower miR-126 but higher miR-21-3p and miR-133a-3p. Only miR-133a-3p exhibited exceptional discriminatory ability between subjects with and without plaque (area under the curve, 0.90; 95% confidence interval, 0.81-0.99).

A specific signature of c-miRNA comprising miR-375, miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p may facilitate CVR monitoring after bariatric surgery. Furthermore, miR-21-3p, miR-126-3p, and miR-133a-3p show potential as specific biomarkers for subclinical atherosclerosis, with miR-133a-3p potentially able to diagnose subclinical atherosclerosis early in severe obesity.

Background and Objectives: Acute ischemic stroke (AIS) is a leading cause of death and disability with poor long-term outcomes. Creating a predictive score for long-term mortality in AIS might be important for optimizing treatment strategies. The aim of this study is to develop and validate a predictive score for three-year mortality in patients with AIS using several demographic, clinical, laboratory and imaging parameters. Materials and Methods: This study included 244 AIS patients admitted to a tertiary center and followed up for three years. The patients' data included demographics, clinical features, laboratory tests (including resistin and leptin levels) and imaging parameters. The patients were randomly divided into a predictive group (n = 164) and a validation group (n = 80). Results: Advanced age, a high NIHSS score, low levels of hemoglobin, elevated resistin levels and the presence of carotid plaques were independently associated with three-year mortality. The predictive model incorporated these variables, and it was validated in a separate cohort. Leptin levels did not significantly predict mortality. Conclusions: This study developed and validated a promising predictive score for three-year mortality in patients with AIS. Advanced age, high NIHSS scores, low hemoglobin levels, elevated resistin levels and the presence of carotid plaques were the independent predictors of long-term mortality.

Carbohydrate-responsive element-binding protein (ChREBP) is a transcription factor that regulates several metabolic genes, including the lipogenic enzymes necessary for the metabolic conversion of carbohydrates into lipids. Although the crucial role of ChREBP in the liver, the primary site of de novo lipogenesis, has been studied, its functional role in adipose tissues, particularly brown adipose tissue (BAT), remains unclear. In this study, we investigated the role of ChREBP in BAT under conditions of a high-carbohydrate diet (HCD) and ketogenic diet (KD), represented by extremely low carbohydrate intake.

Using an adeno-associated virus and Cas9 knock-in mice, we rapidly generated Chrebp brown adipocyte-specific knock-out (B-KO) mice, bypassing the necessity for prolonged breeding by using the Cre-Lox system.

We demonstrated that ChREBP is essential for glucose metabolism and lipogenic gene expression in BAT under HCD conditions in Chrebp B-KO mice. After nutrient intake, Chrebp B-KO attenuated the KD-induced expression of several inflammatory genes in BAT.

Our results indicated that ChREBP, a nutrient-sensing regulator, is indispensable for expressing a diverse range of metabolic genes in BAT.