Leptin pathway is a crucial target for anthocyanins to protect against metabolic syndrome.

The high prevalence of metabolic syndrome is threatening the health of populations all over the world. Contemporary work demonstrates that high leptin concentration is directly related to the development of metabolic syndrome such as obesity, fatty liver diseases, type 2 diabetes mellitus and cardiovascular diseases. Anthocyanins are a widespread group of dietary polyphenols, which can ameliorate chronic diseases related to metabolic syndrome. In addition, anthocyanins can regulate the leptin pathway in chronic metabolic diseases, however the potential mechanism between anthocyanin and leptin is complex and elusive. In this review paper, we have evaluated the bioactivity of anthocyanins on the mediation of leptin level and the upstream and downstream pathways in chronic metabolic diseases. Anthocyanins could regulate the hypertrophy of adipose tissue, and the expression of leptin level via mediating TNF-α, C/EBP, PPAR, CREB and SREBP-1. Anthocyanins promoted the leptin sensitivity by increasing the level of leptin receptor, phosphorylation of JAK2/STAT3, PI3K/AKT, and additionally ameliorated metabolic disorder related outcome, including oxidative stress, inflammation, lipid accumulation, insulin resistance and the balance of gut microbiota. However, direct evidence of anthocyanins treatment on leptin signal transduction is still limited which calls for future molecular binding and gene regulation test.

The causal impact of gut microbiota on circulating adipokine concentrations: a two-sample Mendelian randomization study.

PURPOSE: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue. METHODS: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results. RESULTS: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: ß = 0.063, P = 0.034), the genus Butyrivibrio (IVW: ß = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: ß=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: ß=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: ß=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: ß = 0.235, P = 0.03) and the order Clostridiales (IVW: ß = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: ß = 0.953, P = 0.022) and the order Lactobacillales (IVW: ß=-0.806, P = 0.042) were suggestive of an association with PAI-1. CONCLUSION: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

Ironing out obesity.

Obesity is associated with dysfunctions in hypothalamic neurons that regulate metabolism, including agouti-related protein (AgRP)-expressing neurons. In a recent article, Zhang et al. demonstrated that either diet- or genetically induced obesity promoted iron accumulation specifically in AgRP neurons. Preventing iron overload in AgRP neurons mitigated diet-induced obesity and related comorbidities in male mice.

The association between leptin and diabetes: A meta-analysis.

PURPOSE: The study object was to determine the relationship between leptin and diabetes. METHODS: We searched for the literature on the relationship between leptin and diabetes from PubMed, EMBASE, Cochrane Library, and CNKI databases. We carried out the meta-analysis by calculating the Std. Mean Difference (SMD) and 95% confidence intervals (CIs) to study the relationship between leptin and diabetes. We performed the Chi-square-based Q test and I2 statistics to evaluate the potential heterogeneity, and the sensitivity analysis was performed to evaluate the stability of our results. Moreover, Begg's test was performed to evaluate the publication bias. RESULTS: There are 10 studies in this study for meta-analysis, which include 1879 patients (diabetic (n = 1024); and nondiabetic patients (n = 855)). The results indicated that the levels of serum leptin were significantly increased in patients with diabetes (SMD = 1.78, 95% CI [0.81, 2.76]), especially those with gestational diabetes mellitus compared with controls (SMD = 3.03, 95% CI [1.21, 4.86]). However, the results showed that there was no difference in serum leptin levels between type 2 diabetes and controls (SMD = 0.34, 95% CI [-1.06, 1.74]). CONCLUSIONS: Our analysis indicated that the levels of serum leptin were significantly elevated in patients with diabetes especially those with gestational diabetes mellitus compared with controls.

GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.

Interleukin-4 inhibits the hypothalamic appetite control by modulating the insulin-AKT and JAK-STAT signaling in leptin mutant mice.

Our previous research identified interleukin-4 (IL-4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL-4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL-4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti-related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL-4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT-beige switch. In summary, this study uncovers novel function of IL-4 in mediating food-intake behaviors and metabolic efficiency by regulating hypothalamic appetite-control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL-4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders.

Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents: An observational study.

BACKGROUND: Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. OBJECTIVES: In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. METHODS: A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 µM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. RESULTS: GLP-1 was associated with air pollution exposure (NO2 ß* = -0.13, BC ß* = -0.15, PM2.5 ß* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (ß* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin ß* = -0.16; p = 0.04, total ghrelin ß* = -0.23; p = 0.0051) and happiness (active ghrelin ß* = 0.25; p < 0.001, total ghrelin ß* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (ß* = -0.22; p = 0.036). DISCUSSION: Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

Hypertension and diabetes, but not leptin and adiponectin, mediate the relationship between body fat and chronic kidney disease.

PURPOSE: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45-65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. RESULTS: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI -0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI -18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI -7.1; 126.6]). CONCLUSION: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.

Leptin signalling regulates transcriptional differences in granulosa cells from genetically obese mice but not the activation of NLRP3 inflammasome.

Obesity is associated with increased ovarian inflammation and the establishment of leptin resistance. We presently investigated the role of impaired leptin signalling on transcriptional regulation in granulosa cells (GCs) collected from genetically obese mice. Furthermore, we characterised the association between ovarian leptin signalling, the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and macrophage infiltration in obese mice. After phenotype characterisation, ovaries were collected from distinct group of animals for protein and mRNA expression analysis: (i) mice subjected to a diet-induced obesity (DIO) protocol, where one group was fed a high-fat diet (HFD) and another a standard chow diet (CD) for durations of 4 or 16 weeks; (ii) mice genetically deficient in the long isoform of the leptin receptor (ObRb; db/db); (iii) mice genetically deficient in leptin (ob/ob); and (iv) mice rendered pharmacologically hyperleptinemic (LEPT). Next, GCs from antral follicles isolated from db/db and ob/ob mice were subjected to transcriptome analysis. Transcriptional analysis revealed opposing profiles in genes associated with steroidogenesis and prostaglandin action between the genetic models, despite the similarities in body weight. Furthermore, we observed no changes in the mRNA and protein levels of NLRP3 inflammasome components in the ovaries of db/db mice or in markers of M1 and M2 macrophage infiltration. This contrasted with the downregulation of NLRP3 inflammasome components and M1 markers in ob/ob and 16-wk HFD-fed mice. We concluded that leptin signalling regulates NLRP3 inflammasome activation and the expression of M1 markers in the ovaries of obese mice in an ObRb-dependent and ObRb-independent manner. Furthermore, we found no changes in the expression of leptin signalling and NLRP3 inflammasome genes in GCs from db/db and ob/ob mice, which was associated with no effects on macrophage infiltration genes, despite the dysregulation of genes associated with steroidogenesis in homozygous obese db/db. Our results suggest that: (i) the crosstalk between leptin signalling, NLRP3 inflammasome and macrophage infiltration takes place in ovarian components other than the GC compartment; and (ii) transcriptional changes in GCs from homozygous obese ob/ob mice suggest structural rearrangement and organisation, whereas in db/db mice the impairment in steroidogenesis and secretory activity.

Characterization of circulating leptin-receptor levels following acute sleep restriction: A pilot study on healthy adult females.

BACKGROUND: Insufficient sleep adversely affects energy homeostasis by decreasing leptin levels. The underlying physiological mechanisms; however, remain unclear. Circulating leptin is well described to be regulated by its soluble receptor (sOB-R). Intriguingly, the impact of short sleep duration on sOB-R levels has never been characterized. AIM: In this study, we investigated, for the first time, the variation of sOB-R levels and its temporal relationship with circulating leptin upon acute sleep restriction. METHODS: Five adult females were maintained on an 8-hour sleep schedule (bedtime at 00:00) for 1 week before restricting their sleep to 4.5 h (bedtime at 03:30) on 2 consecutive nights. Balanced meals were scheduled to specific hours and sleep was objectively measured. Four-hour blood samples were regularly collected during waking hours between 08:00 and 00:00. RESULTS: Sleep restriction resulted in lower leptin (20.9 ± 1.7 vs 25.7 ± 1.7 ng/ml) and higher sOB-R concentrations (24.4 ± 1.2 vs 19.8 ± 1.6 ng/ml). Neither the discordant temporal relationship nor the pattern of leptin and sOB-R were altered in response to sleep restriction. CONCLUSION: Our results suggest that sleep restriction may modulate circulating leptin levels and possibly metabolism via upregulating its soluble receptor. This observation may have valuable therapeutic implications when considering sOB-R as a potential target during the management of metabolic disturbances.

The 40-min HIIT acutely induced bone formation which was likely through the increases in muscle derived interleukin 6 and adiponectin activation: The 16 weeks of HIIT intervention, longitudinal randomized controlled trial.

PURPOSE: There is some controversy regarding cytokines released from adipocytes, particularly adiponectin, leptin, and IL6 that regulate bone remodeling. In addition, IL6 is released from muscle contraction, which might have a distinct role in bone remodeling. Hence, this study investigated whether muscle contraction during a session of 40 min of high intensity interval training (40-min HIIT) and after 16 weeks of HIIT (16-wk HIIT) altered the release of those cytokines and bone remodeling in overweight women. METHODS: In total, 22 overweight, premenopausal women were randomly assigned to either the exercise or the control group. The exercise participants engaged in the 40-min HIIT session at 80-90 % of their heart rate reserve (HRR) three times weekly for 16 weeks, while the control participants performed their routine daily activities. Blood was drawn after overnight fasting and immediately after completing the 40-min HIIT sessions to investigate the association of adiponectin, leptin, IL6, CTX, and P1NP through the acute effect of the 40-min HIIT sessions. This process was repeated after the 16-wk intervention program to observe the training effect of HIIT on cytokines linkage. The bone mineral density (BMD) levels of the distal tibia, femur, and lumbar spine were determined prior to and after the 16-wk intervention using dual-energy X-ray absorptiometry. RESULTS: The P1NP level increased by 8.29-20.52 % (95 % CI) and by 2.91-15.54 % after completing the first and last bouts of the 40-min HIIT sessions, respectively. In addition, IL6 increased by 13.39-28.03 % (95 % CI), while serum CTX and adiponectin were unaltered from the acute effect of the 40-min HIIT sessions. There was an association between the increases in P1NP and adiponectin (r = 0.682, p = 0.015); however, the increase in P1NP was mostly associated with the increase in IL6 (r = 0.572, p = 0.054) after completing a 40-min HIIT session. After the 16-wk HIIT program, the resting adiponectin level of the exercise participants increased; however, this was associated with neither bone biomarkers nor BMD. The BMDs of the exercise participants were maintained; however, the tibial BMD of the control participants decreased with an increase in the resting CTX level after 16 weeks. CONCLUSION: Muscle contraction during the 40-min HIIT session elevated the IL6 level, which might have subsequently enhanced bone formation. Furthermore, the association between acute changes in adiponectin and P1NP suggested the possibility of an increase in the sensitivity of the adiponectin receptor in osteoblasts.

Association between Toxoplasma gondii and gestational diabetes with regard to serum leptin and tumor necrosis factor alpha, a preliminary study.

Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July-November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii, and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9-21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii, leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers.

Is the leptin/BMI ratio a reliable biomarker for endometriosis?

Background: The aim of this study was to analyze the concentration of leptin in peritoneal fluid and plasma and to assess their role as potential biomarkers in the diagnosis of endometriosis. Materials & methods: Leptin adjusted for BMI (leptin/BMI ratio) was measured using surface plasmon resonance imaging (SPRI) biosensors. Patients with suspected endometriosis were included in the study. Plasma was collected from 70 cases, and peritoneal fluid from 67 cases. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group and a control group (patients without endometriosis). Results: Leptin/BMI ratio in plasma did not differ between women with endometriosis and the control group (0.7159 ± 0.259 vs 0.6992 ± 0.273, p= 0,7988). No significant differences were observed in peritoneal leptin/BMI ratio levels in patients with and without endometriosis (0.6206 ± 0.258 vs 0.6215 ± 0.264, p= 0,9896). Plasma and peritoneal leptin/BMI ratios were significantly lower in women with endometriosis - related primary infertility compared to women with endometriosis without primary infertility (0.640 ± 0.502 vs 0.878 ± 0.623, p < 0.05). The difference was observed in case of primary infertility, but not in terms of the secondary one. No significant differences were noted between leptin/BMI ratio in the proliferative phase and the secretory phase (0.716 ± 0.252 vs 0.697 ± 0.288, p= 0,7785). Conclusion: The results of present study do not support the relevance of leptin concentration determination as a biomarker of the endometriosis. Due to the limited number of samples in the tested group, further studies are needed to confirm its role.

Obesity: An Impact with Cardiovascular and Cerebrovascular Diseases.

The authors sought to correlate the complex sequel of obesity with various parameters known to develop metabolic syndrome viz. insulin resistance, dyslipidemia, hypertension etc., as these anomalies are linked to vascular atherosclerosis and outbreak of cardiovascular and cerebrovascular diseases.  A comprehensive online survey using MEDLINE, Scopus, PubMed and Google Scholar was conducted for relevant journals from 1970 till present time (2023) with key search terms like: 'obesity', 'leptin', type-2 diabetes', 'atherosclerosis', 'cardiovascular and cerebrovascular diseases'. The findings of the reports were compared and correlated. The information was then collated for developing this review. Reports showed that in human obesity, hyper-leptinemia could induce hyperglycemia, which in turn templates hypercholesterolemia. Persisting hypercholesterolemia over a period of time may en-route atherosclerosis in blood vessels. Thus obesity has been considered as a template for originating hyperglycemia, hypercholesterolemia and outbreak of vascular atherogenesis or in other words, obesity in long run can trigger atherosclerosis and its related disorders e.g. heart attack and stroke. Literature survey shows that primarily, co-morbidities of human obesity start with leptin and insulin resistance and then multiplies with metabolic irregularities to an extreme that results in pathogenesis of heart attack and stroke. Atherosclerosis associated cardiovascular and cerebrovascular events are independent risks of obese subjects and particularly in the cases of persisting obesity.

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer.

Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including 'EOCRC', 'obesity', 'obesity-related hormones', 'itaconate', 'adiponectin', 'leptin', 'M2a macrophage', and 'microbiome'. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.

Study of association of leptin with leukocyte telomere length in a Chinese rural population.

BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for ß-Cell Function (HOMA-ß), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-ß, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-ß, ΔQUICKI, and ΔLEP do not affect ΔRLTL. CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Acupoints catgut embedding recovers leptin resistance via improving autophagy progress mediated by AMPK-mTOR signaling in obese mice.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

Predictors of weight and waist gain in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Background: Weight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, a high-risk group known to develop chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. Objective: The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of US South Asians, a high-risk group for developing obesity-related complications. Methods: We used data from Mediators of Atherosclerosis in South Asians Living in America study (MASALA) exam 1 (2010-2013) and exam 2 (2015-2018), with a mean 4.8 years of follow-up. Results: Of 634 participants studied (42.7% women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7% had gained ≥5% weight and 32.3% gained ≥5% waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female, employed full or part time, or retired were associated with lower odds of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level were associated with higher odds of waist gain. Conclusions: South Asian subgroups with higher risk of weight and/or waist gain may benefit from targeted interventions to improve health outcomes.

Central leptin signaling deficiency induced by leptin receptor antagonist leads to hypothalamic proteomic remodeling.

AIMS: Leptin irresponsiveness, which is often associated with obesity, can have significant impacts on the hypothalamic proteome of individuals, including those who are lean. While mounting evidence on leptin irresponsiveness has focused on obese individuals, understanding the early molecular and proteomic changes associated with deficient hypothalamic leptin signaling in lean individuals is essential for early intervention and prevention of metabolic disorders. Leptin receptor antagonists block the binding of leptin to its receptors, potentially reducing its effects and used in cases where excessive leptin activity might be harmful. MATERIALS AND METHODS: In this work, we blocked the central actions of leptin in lean male adult Wistar rat by chronically administering intracerebroventricularly the superactive leptin receptor antagonist (SLA) (D23L/L39A/D40A/F41A) and investigated its impact on the hypothalamic proteome using label-free sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for quantitative proteomics. KEY FINDINGS: Our results show an accumulation of proteins involved in mRNA processing, mRNA stability, and translation in the hypothalamus of SLA-treated rats. Conversely, hypothalamic leptin signaling deficiency reduces the representation of proteins implicated in energy metabolism, neural circuitry, and neurotransmitter release. SIGNIFICANCE: The alterations in the adult rat hypothalamic proteome contribute to dysregulate appetite, metabolism, and energy balance, which are key factors in the development and progression of obesity and related metabolic disorders. Additionally, using bioinformatic analysis, we identified a series of transcription factors that are potentially involved in the upstream regulatory mechanisms responsible for the observed signature.

Peripheral biomarkers as a predictor of poor prognosis in severe cases of COVID-19.

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels of COVID-19 patients. We also realized statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. An oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19, as well as correlates between them. Early monitoring of these biomarkers may conduct the correct clinical intervention associated with the clinical symptoms for treating patients infected by SARS-CoV-2.