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Previous reports have described a statistical association between high-density lipoproteins (HDL) subclasses and the expression of genes coding for pro-calcifying proteins in the epicardial adipose tissue of patients with coronary artery disease (CAD) and aortic valvular stenosis (AVS). These results suggest a causal relationship between HDL and the regulation of gene expression in epicardial adipose tissue. However, there is no experimental evidence that supports this causal relationship. Therefore, we explored the effect of HDL isolated from CAD or AVS patients on the expression of OPN, BMP2, and BMP4, genes coding for proteins related to calcification, osteopontin, and bone morphogenetic proteins -2 and -4, respectively, and LEP, UCP, and PER, coding for leptin, uncoupling protein-1, and perilipin-2, respectively, proteins that confer phenotypic characteristics to adipocytes. The experiments were performed using a novel model of cardiac adipocytes differentiated in vitro from stromal cells of rabbit cardiac adipose tissue. AVS or CAD patients' HDL differentially modulated the expression of BMP4 and LEP, whereas HDL from both kinds of patients upregulated the OPN gene expression. A high concentration of triglycerides associated to small HDL and a higher concentration of phospholipids of large HDL from CAD patients than those from AVS individuals were the most remarkable structural differences. Finally, we demonstrated that cholesterol from reconstituted HDL was internalized to the adipocytes. The regulation of genes related to the secretory activity of cardiac adipocytes mediated by HDL has clinical implications as a potential therapeutic target for the prevention and treatment of CAD and AVS. In summary, the HDL isolated from the CAD and AVS patients differentially regulated gene expression in adipocytes by a mechanism that seems to be dependent on HDL lipid internalization to the cells and structural characteristics of the lipoproteins.

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Up to 30% of individuals with obesity may exhibit normal insulin sensitivity, a favorable lipid profile, and no signs of hypertension. This prompts the exploration of factors distinguishing cardiometabolically healthy individuals from those developing complications. This cross-sectional study included 116 individuals categorized into four groups by combining abdominal obesity and cardiometabolic health statuses. We compared circulating adipokines and gut microbiota composition between these groups. Individuals with abdominal obesity had higher levels of hs-CRP, TNF-α, MCP-1, IL-18, chemerin, and leptin, and a less favorable gut microbiota composition, including higher levels of potentially harmful bacteria (CAG-Pathogen) and lower levels of beneficial bacteria (CAG-Ruminococcaceae and CAG-Akkermansia), compared to those with adequate waist circumference. Those with obesity but cardiometabolically healthy displayed similar adipokine levels and microbiota composition to those with adequate waist. In contrast, individuals with abdominal obesity cardiometabolically abnormal exhibited significantly higher levels of hs-CRP, IL-18, chemerin, and leptin, and lower levels of adiponectin and CAG-Ruminococcaceae compared to those with abdominal obesity cardiometabolically healthy and adequate waist. Additionally, they differed in hs-CRP and adiponectin/leptin ratio from individuals with obesity cardiometabolically healthy. These findings suggest that altered adipokine profiles and gut microbiota may contribute to the development or persistence of cardiometabolic complications in obesity.

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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.

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OBJECTIVE: To describe independent factors related to the interaction of FTO rs9939609, TMEM18 rs6548238, leptin, and adiponectin in children/adolescents with asthma, under the influence of obesity. METHODS: The authors performed a cross-sectional study with 57 children/adolescents, ages 8-19 years, at a tertiary hospital, from 2017 to 2018. Participants were classified by nutritional status, performed spirometry with a bronchodilator test and completed an asthma questionnaire, higher scores indicated more asthma symptoms. Two asthma groups were formed: Group 1(G1)-normal-weight; Group 2(G2)-overweight/obese. Serum was collected for adipokines (n = 32) and genetic polymorphisms (n = 53) dosages. RESULTS: Age and body mass index (BMI) correlated directly in normal-weight (p = 0.009) and obese participants (p = 0.004). Girls reported more asthma complaints (p = 0.044). Participants with negative bronchodilator responses presented lower BMI (14.55-17.16) than responders (19.4-26.84) (p = 0.049). Leptin dosages are related directly to BMI (5,34-40 ng/ml in obese × 0,54-42 ng/ml in nonobese) (p = 0.003). Levels were high in girls (4.78-17.55 µg/ml) (p = 0.029) and low in nonobese boys (0.54-6.92 µg/ml) (p = 0.006). In obese, low leptin levels (< 10 ng/ml) were found in small airway dysfunction carriers (p = 0.025); elevated adiponectin (> 5 µg/ml) correlated with FEV1/FVC > 80 % (p = 0.035) and positive bronchodilator tests (8.84-13 µg/ml) (p = 0.039); and FTO A allele correlated with low adiponectin 0-8.84 µg/ml (p = 0.021) and low FEV1/FVC (46 %-88 %) (p = 0.023). CONCLUSION: BMI correlated directly with age and leptin levels. Obese participants presented high serum levels of leptin and FTO A allele correlated with low FEV1/FVC. Larger cohorts are necessary for better elucidation of the role of adipokines and polymorphisms in the pathophysiology of asthma and obesity.

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Obesity is a disorder of multifactorial origin in which both genetic and environmental factors intervene. Currently, numerous gene variants related to the control of intake and the mechanism of action of leptin in the central nervous system through the melanocortin pathway have been described. The accessibility to molecular studies through next-generation sequencing panels that include dozens of genes related to this condition shows that the incidence is much higher than previously reported. This review intended to provide information on the diagnostic procedures and therapeutic interventions available specifically for the management of hyperphagia and obesity in affected patients. Early recognition of syndromic and non-syndromic monogenic obesity avoids the indication of risky interventions with no longterm benefit such as surgery and non-specific drugs. The presence of early severe obesity and hyperphagia, together with neurodevelopmental, metabolic and endocrine disorders should lead to the request of genetic studies in search of a definitive diagnosis.

La obesidad es un trastorno de origen multifactorial en el que intervienen factores tanto genéticos como ambientales. En la actualidad se han descrito numerosas variantes génicas relacionadas con el control de la ingesta y con el mecanismo de acción de la leptina en el sistema nervioso central a través de la vía de las melanocortinas. La accesibilidad a estudios moleculares por medio de paneles de secuenciación de nueva generación que incluyen decenas de genes relacionados a esta condición, muestra que la incidencia es muy superior a lo previamente reportado. Esta revisión tiene como objetivo brindar información sobre los procedimientos diagnósticos y las intervenciones terapéuticas disponibles específicamente para el control de la hiperfagia y la obesidad en los pacientes afectados. El reconocimiento temprano de la obesidad monogénica sindrómica y no sindrómica evita la indicación de intervenciones riesgosas sin beneficio a largo plazo como cirugías y fármacos no específicos. La presencia de obesidad grave temprana e hiperfagia, junto a alteraciones del neurodesarrollo, metabólicas y endócrinas deben llevar a la solicitud de estudios genéticos en busca de un diagnóstico definitivo.

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A large number of studies have reported the relationships between leptin levels and diabetes or obesity. However, the results are still controversial, and no consensus has been reached. Therefore, the purpose of the study was to collect data from various databases to perform a meta-analysis and address the inconsistencies in these studies. A systematic literature search was conducted on PubMed, Web of Science, and EBSCO for relevant available articles. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the association by a meta-analysis. Fifteen reports with 1,388 cases and 3,536 controls were chosen for the meta-analysis. First, an increase in leptin levels in serum (SMD 0.69; 95% CI 0.36-1.02 ng/mL) and plasma (SMD 0.46; 95% CI 0.18-0.74 ng/mL) was observed in individuals with diabetes compared to controls. This increased level was also observed by gender and population. Second, statistical analysis showed that leptin levels in serum were significantly increased in individuals with obesity (SMD 1.03; 95% CI 0.72-1.34 ng/mL). This meta-analysis analyzed leptin in individuals with diabetes or obesity and emphasized the importance of monitoring serum/plasma leptin levels in patients with these diseases. However, more comprehensive studies are necessary in order to draw firm conclusions.

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INTRODUCTION: Adiponectin and leptin play important roles in the central nervous system. During the postpartum period, there is a need for a better understanding of the relationship between these cytokines and the neurological development of the infant, as well as their influence on preventing maternal depressive symptoms. OBJECTIVES: To assess the correlation between adiponectin and leptin in maternal plasma and breast milk and their association with: infant neurodevelopment at 6 and 12 months of age; and maternal mental health over the first year postpartum. METHODS: Prospective cohort study with four follow-up. Mothers and their newborns are recruited within the first 15 days postpartum (baseline). Follow-up visits occur at 2, 6, and 12 months postpartum. Visits include blood and breast milk collection, application of the Edinburgh Postnatal Depression Scale and Beck Depression Inventory to assess maternal mental health, application of the Bayley-III scale for infant developmental assessment, maternal and infant anthropometry and body composition, evaluation of reproductive history, mother-infant bonding, breastfeeding, consumption of ultra-processed foods, sleep quality, and socio-economic and demographic data. RESULTS: The research received funds in August 2022, and participant recruitment began in September 2022. The sample size will consist of 95 mother-child pairs. As of September 2023, 68 participants have been recruited. CONCLUSION: The project will provide insights into the association between adiponectin and leptin with postpartum depression and infant neurodevelopment, ultimately promoting improved care and quality of life for these groups. Additionally, it will provide data on the type of delivery, infant physical growth, maternal and infant body composition changes, sleep quality, consumption of ultra-processed foods, and maternal metabolic health, including vitamin D metabolites, oxidized polyunsaturated fatty acid metabolites, phospholipid species and triacylglycerols, which are of significant relevance to public health and, when interconnected, may yield important results and contribute to the existing literature. TRIAL REGISTRATION: Name of the registry: Brazilian Clinical Trials Registry (ReBec). Registration number: RBR-9hcby8c.

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High neonatal growth hormone (GH) secretion has been described in several species. However, the neuroendocrine mechanisms behind this surge remain unknown. Thus, the pattern of postnatal GH secretion was investigated in mice and rats. Blood GH levels were very high on postnatal day (P)1 and progressively decreased until near zero by P17 in C57BL/6 mice without sex differences. This pattern was similar to that observed in rats, except that female rats showed higher GH levels on P1 than males. In comparison, follicle-stimulating hormone exhibited higher secretion in females during the first 3 weeks of life. Hypothalamic Sst mRNA and somatostatin neuroendocrine terminals in the median eminence were higher in P20/P21 mice than in newborns. Knockout mice for GH-releasing hormone (GHRH) receptor showed no GH surge, whereas knockdown mice for the Sst gene displayed increased neonatal GH peak. Leptin deficiency caused only minor effects on early-life GH secretion. GH receptor ablation in neurons or the entire body did not affect neonatal GH secretion, but the subsequent reduction in blood GH levels was attenuated or prevented by these genetic manipulations, respectively. This phenotype was also observed in knockout mice for the insulin-like growth factor-1 (IGF-1) receptor in GHRH neurons. Moreover, glucose-induced hyperglycemia overstimulated GH secretion in neonatal mice. In conclusion, GH surge in the first days of life is not regulated by negative feedback loops. However, neonatal GH secretion requires GHRH receptor, and is modulated by somatostatin and blood glucose levels, suggesting that this surge is controlled by hypothalamic-pituitary communication.

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Osteoporosis and obesity are prevalent diseases in menopause. The phytoestrogen genistein (Gen) is an antioxidant/anti-inflammatory agent proposed as natural therapy to counteract syndromes associated to menopause. In this work we evaluated the bone effect of Gen in a stress environment induced by hypoestrogenism and obesity. Bilaterally ovariectomized female Wistar rats were fed with high-fat diet (obese), or standard diet (non-obese). Osteoblasts (OB) primary cultures from femoral shafts, and retroperitoneal explants of white adipose tissue (WAT) in vitro exposed to Gen were employed as experimental systems. In obese rats, bone oxidative stress revealed by enhancement on H2O2 release, and significant reduction in OB nitric oxide (NO) production, cell growth, alkaline phosphatase activity (ALP), matrix mineralization and collagen deposition was detected. In OB-WAT co-cultures, Gen treatment inhibited H2O2 secretion, and prompted OB differentiation. A direct action of Gen on WAT was demonstrated. The phytoestrogen inhibited H2O2 and TBARS production, and diminished the secretion of the inflammatory adipokine leptin, through a mechanism of action mediated by estrogen receptor (ER) involvement, and MAPK and PI3K signal transduction pathways participation. A directional interaction from WAT to bone was evidenced by the incubation OB with conditioned medium obtained from WAT exposed to Gen (Gen-CM). The presence of Gen-CM improved OB growth, and reduced H2O2 production. The antioxidative effect of Gen on obese bone cells was partially dependent on its ability to reduce leptin secretion by WAT. Altogether, the results suggest that, under obesity, Gen may improve bone metabolism through a direct action on WAT.

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BACKGROUND: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. METHODS: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. RESULTS: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. CONCLUSIONS: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

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PURPOSE: Hibiscus sabdariffa (HS) extract has several health benefits and anti-obesogenic effects. The aim of the present study was to assess whether the medicinal properties attributable to HS would prevent or mitigate bladder changes induced by obesity in an experimental model. METHODS: Forty-eight male Wistar rats were submitted to one of four different dietary interventions (12 animals each): G1, standard diet and water (controls); G2, standard diet and HS tea; G3, a palatable high-fat diet and water; and G4, high-fat diet diet and HS tea. The animals were monitored for body weight, feed, and water and tea intake, according to the allocated group. After 16 weeks, the animals were euthanized, and the levels of creatinine, inflammatory cytokines, testosterone, cholesterol, triglycerides, and electrolytes were evaluated. In addition, histopathological analysis of the animals' bladder was performed. RESULTS: Groups receiving HS (G2 and G4) showed decreased levels of the pro-inflammatory cytokine interleukin-1α. HS tea was able to reduce low-density lipoprotein and triglyceride levels in the G2 group compared to other groups. Only in the G3 there was a significant increase in the body weight when it was compared the 12th and 16th weeks. Leptin was shown to be elevated in the groups that received a high-fat diet. There was a significant decrease in the muscle fibers thickness and in the total collagen count in G4 bladder when compared with G1 and G3. CONCLUSIONS: HS has an anti-inflammatory role, can reverse hyperlipidemia in rats, and reduced deleterious effects of obesity on these animals' bladder.

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OBJECTIVE: Glucagon-like peptide-1 (GLP1) and leptin (Lep) are afferent signals that regulate energy metabolism. Lactational hypernutrition results in hyperphagia and adiposity in adult life, and these events can be prevented by exercise. We evaluated the effects of swimming training on hypothalamic (GLP1-R) and Lep receptor (Lep-R) gene expressions in lactational hypernutrition-induced obesity. METHODS: On the 3rd postnatal day, the litter sizes of lactating dams were adjusted to small litters (SL; 3 pups/dams) or normal litters (NL; 9 pups/dams). After weaning (21 days), NL and SL male rats were randomly distributed to sedentary (Sed) and exercised (Exe) groups. Exercised mice swam (30 min/3 times/week) for 68 days. Food intake and body weight gain were registered. At 92 days, intraperitoneal glucose and insulin tolerance tests were performed and rats were euthanized at 93 days; adipose tissue depots were weighed, and blood counts and plasma biochemical analyses performed. Hypothalamus were isolated to evaluate Lep-R and GLP1-R gene expressions. RESULTS: Small litters sedentary rats presented increased body weight gain, adiposity, insulin sensibility and higher fasting values of glucose and triglycerides, besides higher hypothalamic gene expressions of Lep-R and GLP1-R, compared to NLSed animals. SLExe rats did not develop obesity or metabolic abnormalities and Lep-R and GLP1-R hypothalamic gene expressions were normalized. CONCLUSION: Lactational hypernutrition induces obesity and metabolic dysfunction in adult life, in association with higher hypothalamic expressions of the Lep-R and GLP1-R genes. Exercise prevented obesity and improved metabolic state in SL overnourished rats, and normalized their hypothalamic Lep-R and GLP1-R gene expressions.

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Background: Metabolic syndrome (MetS) in children is a rising health issue that is strongly associated with cardiovascular diseases and type 2 diabetes mellitus development. Low-affinity antibodies reactive to leptin and ghrelin are suggested to regulate hormone stability and function; nevertheless, the role of the leptin/ghrelin axis and antibodies reactive to both hormones in relation to MetS or its components in the pediatric population remains unknown. Methods: Fifty-eight children (7-12 years) were included and categorized according to the presence of one or more criteria for the diagnosis of MetS or according to body mass index. Body composition, biochemical variables, and metabolic risk indexes were determined. Antibodies reactive to leptin and ghrelin were quantified by an in-house enzyme-linked immunosorbent assay test. Ratios of leptin/ghrelin hormones and anti-leptin/anti-ghrelin immune complexes were obtained. Results: The biochemical variables glucose (P = 0.0009), insulin (P = 0.0001), leptin (P = 0.0036), HOMA-IR (homeostatic model assessment for insulin resistance) (P < 0.0001), and plasma atherogenic index (P < 0.0001) were significantly higher in children with two or three components of MetS (MetS 2-3) in comparison to children with none or one component (MetS 0-1). Ratios of leptin/ghrelin (P = 0.0307) and anti-leptin/anti-ghrelin immune complexes (P = 0.0338) were higher in MetS 2-3 group versus MetS 0-1 group. In MetS 2-3 group, both insulin (r = 0.4361, P = 0.0293) and HOMA-IR (r = 0.4761, P = 0.0161) were positively correlated with the leptin/ghrelin hormone ratio. Conclusions: The higher leptin/ghrelin hormone ratio scores observed in MetS 2-3 group, along with their correlation with insulin levels and HOMA-IR, highlight the role of leptin and ghrelin on insulin sensitivity and metabolic regulation. An increased ratio of anti-leptin/anti-ghrelin immune complexes suggests affinity changes in these antibodies that may lead to alterations in hormone function.

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AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.

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Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

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During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed toward the relevance of hypoxia as modulator of trophoblast cell death. Previous reports have shown that leptin, a placental cytokine, promotes cell survival in both cell culture and placental explant models. The aim of this work is to establish the role of leptin in apoptosis under hypoxic condition in trophoblast cells. In this study, we evaluated the effect of cobalt chloride, a hypoxia mimicking agent that stabilizes the expression of hypoxia-inducible factor-1 alpha, on Swan-71 and human placental explants. Hypoxia chamber was also used to generate 2% oxygen. Apoptosis was determined by the presence of apoptotic nucleus, fragmentation of DNA and Caspase-3 and PARP-1 cleavage. The pro-apoptotic proteins BAX, BID, BAD, and BAK and the anti-apoptotic effectors BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1 were also analyzed. We found that hypoxia-inducible factor-1 alpha stabilization increased the appearance of apoptotic nucleus, fragmentation of DNA, and Caspase-3 and PARP-1 cleavage. Hypoxia mimicking conditions enhanced the expression of pro-apoptotic effectors BAX, BID, BAD, and BAK. Hypoxia-inducible factor-1 alpha stabilization also downregulated the level of BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1. All these apoptotic parameters changes were reversed with leptin treatment. Moreover, we showed that leptin action on apoptosis modulation involves PI3K and MAPK signaling pathways. Obtained data demonstrate that hypoxia-inducible factor-1 alpha stabilization induces apoptosis in human placenta and leptin counteracts this effect, reinforcing its role as a survival cytokine.

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Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (LEPR), suppressor of cytokine signaling 3 (SOCS3), sterol regulatory element-binding transcription factor 1 (SREBF1), stearoyl-CoA desaturase-1 (SCD1), and patatin-like phospholipase domain-containing protein 2 (PNPLA2), were determined from liver and adipose tissue. Higher serum leptin and LEPR levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, LEPR was positively correlated with leptin expression in adipose tissue, and SOCS3 was correlated with SREBF1-SCD1. In OAT, SOCS3 was correlated with insulin resistance and transaminase enzymes (p < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.

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Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM2.5) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD). PM2.5 contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low-and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM2.5 exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.

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BACKGROUND: The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. OBJECTIVES: This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. SETTING: Public hospital, Brazil. METHODS: Forty-eight women with severe obesity (20-59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). RESULTS: The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = -.418, P = .038), WC (r = -.437, P = .029), and glycated hemoglobin (HbA1C) (r = -.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015). CONCLUSIONS: The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.