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Cardiovascular Research Dec 2023Obesity is an epidemic that is a critical contributor to hypertension and other cardiovascular diseases. Current paradigms suggest that endothelial nitric oxide synthase...
AIMS
Obesity is an epidemic that is a critical contributor to hypertension and other cardiovascular diseases. Current paradigms suggest that endothelial nitric oxide synthase (eNOS/NOS3) in the vessel wall is the primary regulator of vascular function and blood pressure. However, recent studies have revealed the presence of eNOS/NOS3 in the adipocytes of white adipose tissues and perivascular adipose tissues (PVATs). The current understanding of the role of adipocyte NOS3 is based mainly on studies using global knockout models. The present study aimed to elucidate the functional significance of adipocyte NOS3 for vascular function and blood pressure control.
METHODS AND RESULTS
We generated an adipocyte-specific NOS3 knockout mouse line using adiponectin promoter-specific Cre-induced gene inactivation. Control and adipocyte-specific NOS3 knockout (A-NOS3 KO) mice were fed a high-fat diet (HFD). Despite less weight gain, A-NOS3 KO mice exhibited a significant increase in blood pressure after HFD feeding, associated with exacerbated vascular dysfunction and remodelling. A-NOS3 KO mice also showed increased expression of signature markers of inflammation and hypoxia in the PVATs. Among the differentially expressed adipokines, we have observed an upregulation of a novel adipokine, chemerin, in A-NOS3 KO mice. Chemerin was recently reported to link obesity and vascular dysfunction. Treatment with chemerin neutralizing antibody normalized the expression of remodelling markers in the aorta segments cultured in serum from HFD-fed A-NOS3 KO mice ex vivo.
CONCLUSION
These data suggest that NOS3 in adipocytes is vital in maintaining vascular homeostasis; dysfunction of adipocyte NOS3 contributes to obesity-induced vascular remodelling and hypertension.
Topics: Animals; Mice; Adipocytes; Adipokines; Chemokines; Diet, High-Fat; Hypertension; Intercellular Signaling Peptides and Proteins; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Obesity; Vascular Remodeling
PubMed: 37897505
DOI: 10.1093/cvr/cvad164 -
Minerva Obstetrics and Gynecology Oct 2023Polycystic ovarian syndrome (PCOS) affects 5-20% of females and is the most common cause of anovulatory infertility. Leptin seems to have an important role in... (Review)
Review
INTRODUCTION
Polycystic ovarian syndrome (PCOS) affects 5-20% of females and is the most common cause of anovulatory infertility. Leptin seems to have an important role in reproduction. Many reproductive pathologies such as preeclampsia, PCOS, and endometriosis are associated to plasma adiponectin levels. Kisspeptin levels are increased in PCOS women.
EVIDENCE ACQUISITION
A review of the literature was completed through the PubMed database aiming to find articles regarding leptin, adiponectin and kisspeptin and if they are related to PCOS pathogenesis.
EVIDENCE SYNTHESIS
Even today it is not clear what is the role of leptin in women with PCOS, although most of the researchers found increased levels of leptin as well as leptin resistance in PCOS (both obese and lean individuals). Many more longitudinal studies should be done to discover the usefulness of measuring adiponectin in prepubertal women who apparently have a possibility to develop PCOS to find out if they finally develop PCOS. Most of the researchers found that PCOS women have decreased levels of adiponectin unrelated to BMI levels. Nevertheless, not all studies had the same result. Moreover, it is necessary more studies to be made to investigate the connection between kisspeptin and other metabolic factors such as LH and insulin resistance.
CONCLUSIONS
In general, it remains inconclusive whether leptin, adiponectin, and kisspeptin can be used as clinical and/or biochemical markers of PCOS. Therefore, it is essential to review the current data with regards to the association between PCOS and circulating leptin, adiponectin, and kisspeptin in women with PCOS.
Topics: Female; Humans; Leptin; Adiponectin; Polycystic Ovary Syndrome; Kisspeptins; Obesity
PubMed: 36255161
DOI: 10.23736/S2724-606X.22.05139-9 -
Cardiovascular Diabetology Dec 2023The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for...
BACKGROUND
The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment.
METHODS AND RESULTS
A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways.
CONCLUSION
The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks.
Topics: Female; Humans; Male; Abdominal Fat; Adipokines; Adipose Tissue; Biomarkers; Body Mass Index; Intra-Abdominal Fat; Obesity; Subcutaneous Fat; Thrombospondins
PubMed: 38066623
DOI: 10.1186/s12933-023-02075-0 -
Molecular Medicine Reports Jun 2024Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co‑morbidities, including type‑2 diabetes mellitus (T2DM),... (Review)
Review
Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review).
Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co‑morbidities, including type‑2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non‑alcoholic fatty liver disease, kidney diseases, respiratory disorders, sleep apnea, musculoskeletal disorders and osteoarthritis, subfertility, psychosocial problems and certain types of cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro‑inflammatory polarization of macrophages toward the M1 phenotype, in adipose tissue (AT), with subsequent increased production of pro‑inflammatory cytokines and adipokines, inducing therefore an overall, systemic, low‑grade inflammation, which contributes to metabolic syndrome (MetS), insulin resistance (IR) and T2DM. Targeting inflammatory mediators could be alternative therapies to treat obesity, but their safety and efficacy remains to be studied further and confirmed in future clinical trials. The present review highlights the molecular and pathophysiological mechanisms by which the chronic low‑grade inflammation in AT and the production of reactive oxygen species lead to MetS, IR and T2DM. In addition, focus is given on the role of anti‑inflammatory agents, in the resolution of chronic inflammation, through the blockade of chemotactic factors, such as monocytes chemotractant protein‑1, and/or the blockade of pro‑inflammatory mediators, such as IL‑1β, TNF‑α, visfatin, and plasminogen activator inhibitor‑1, and/or the increased synthesis of adipokines, such as adiponectin and apelin, in obesity‑associated metabolic dysfunction.
Topics: Humans; Obesity; Metabolic Syndrome; Inflammation; Insulin Resistance; Adipokines; Adipose Tissue; Diabetes Mellitus, Type 2; Inflammation Mediators
PubMed: 38606791
DOI: 10.3892/mmr.2024.13219 -
Cardiovascular Diabetology Aug 2023Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin,...
BACKGROUND
Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures.
METHODS
Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT.
RESULTS
In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [β(SE) = 0.060 (0.016), p = 2.52 × 10], and female-specific associations were between cIMT and adiponectin [β(SE) = 0.010 (0.005), p = 0.043] and ARI [β(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [β(SE) = 0.127 (0.015), p = 4.70 × 10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [β(SE) = 0.014 (0.005), p = 0.012 for adiponectin; β(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1].
CONCLUSION
Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.
Topics: Female; Male; Humans; Middle Aged; Adipokines; Leptin; Resistin; Adiponectin; Carotid Intima-Media Thickness; Cross-Sectional Studies; Hispanic or Latino; Atherosclerosis
PubMed: 37653519
DOI: 10.1186/s12933-023-01968-4 -
Diabetes, Obesity & Metabolism Nov 2023One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which may result in significant health threats of the mother, fetus and the...
AIMS
One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which may result in significant health threats of the mother, fetus and the newborn. Fatty acid-binding protein 4 (FABP4) is an adipokine that regulates glucose homeostasis by promoting glucose production and liver insulin resistance in mouse models. FABP4 levels are increased in GDM and correlates with maternal indices of insulin resistance, with a rapid decline post-partum. We therefore aimed to determine the tissue origin of elevated circulating FABP4 levels in GDM and to assess its potential contribution in promoting glucagon-induced hepatic glucose production.
MATERIALS AND METHODS
FABP4 protein and gene expression was determined in biopsies from placenta, subcutaneous (sWAT) and visceral (vWAT) white adipose tissues from GDM and normoglycaemic pregnant women. FABP4 differential contribution in glucagon-stimulated hepatic glucose production was tested in conditioned media before and after its immune clearance.
RESULTS
We showed that FABP4 is expressed in placenta, sWAT and vWAT of pregnant women at term, with a significant increase in its secretion from vWAT of women with GDM compared with normoglycaemic pregnant women. Neutralizing FABP4 from both normoglycaemic pregnant women and GDM vWAT secretome, resulted in a decrease in glucagon-stimulated hepatic glucose production.
CONCLUSIONS
This study provides new insights into the role of adipose tissue-derived FABP4 in GDM, highlighting this adipokine, as a potential co-activator of glucagon-stimulated hepatic glucose production during pregnancy.
Topics: Animals; Female; Humans; Infant, Newborn; Mice; Pregnancy; Adipokines; Adipose Tissue; Diabetes, Gestational; Fatty Acid-Binding Proteins; Glucagon; Glucose; Insulin Resistance; Liver
PubMed: 37449442
DOI: 10.1111/dom.15214 -
Nutrients Apr 2024Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an... (Review)
Review
Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an effective approach for controlling or preventing obesity. This review aims to summarize the experimental method used to study probiotics and obesity, and recent advances in probiotics against obesity. In particular, we focused on studies (in vitro and in vivo) that used probiotics to treat obesity and its associated comorbidities. Several in vitro and in vivo (animal and human clinical) studies conducted with different bacterial species/strains have reported that probiotics promote anti-obesity effects by suppressing the differentiation of pre-adipocytes through immune cell activation, maintaining the Th1/Th2 cytokine balance, altering the intestinal microbiota composition, reducing the lipid profile, and regulating energy metabolism. Most studies on probiotics and obesity have shown that probiotics are responsible for a notable reduction in weight gain and body mass index. It also increases the levels of anti-inflammatory adipokines and decreases those of pro-inflammatory adipokines in the blood, which are responsible for the regulation of glucose and fatty acid breakdown. Furthermore, probiotics effectively increase insulin sensitivity and decrease systemic inflammation. Taken together, the intestinal microbiota profile found in overweight individuals can be modified by probiotic supplementation which can create a promising environment for weight loss along enhancing levels of adiponectin and decreasing leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-β on human health.
Topics: Probiotics; Humans; Obesity; Animals; Gastrointestinal Microbiome; Adipogenesis; Anti-Inflammatory Agents; Inflammation; Adipokines
PubMed: 38732619
DOI: 10.3390/nu16091373 -
Journal of Periodontal Research Jun 2024Lipotoxicity refers to the accumulation of lipids in tissues other than adipose tissue (body fat). It is one of the major pathophysiological mechanisms responsible for... (Review)
Review
Lipotoxicity refers to the accumulation of lipids in tissues other than adipose tissue (body fat). It is one of the major pathophysiological mechanisms responsible for the progression of diabetes complications such as non-alcoholic fatty liver disease and diabetic nephropathy. Accumulating evidence indicates that lipotoxicity also contributes significantly to the toxic effects of diabetes on periodontitis. Therefore, we reviewed the current in vivo, in vitro, and clinical evidence of the detrimental effects of lipotoxicity on periodontitis, focusing on its molecular mechanisms, especially oxidative and endoplasmic reticulum stress, inflammation, ceramides, adipokines, and programmed cell death pathways. By elucidating potential therapeutic strategies targeting lipotoxicity and describing their associated mechanisms and clinical outcomes, including metformin, statins, liraglutide, adiponectin, and omega-3 PUFA, this review seeks to provide a more comprehensive and effective treatment framework against diabetes-associated periodontitis. Furthermore, the challenges and future research directions are proposed, aiming to contribute to a more profound understanding of the impact of lipotoxicity on periodontitis.
Topics: Humans; Periodontitis; Oxidative Stress; Endoplasmic Reticulum Stress; Inflammation; Adipokines; Animals; Diabetes Complications; Diabetes Mellitus; Ceramides; Lipid Metabolism
PubMed: 38419425
DOI: 10.1111/jre.13242 -
BMC Pulmonary Medicine Jan 2024The role of adipokines in the development of lung diseases is significant, yet their specific relationship with different lung diseases remains unclear.
BACKGROUND
The role of adipokines in the development of lung diseases is significant, yet their specific relationship with different lung diseases remains unclear.
METHODS
In our research, we analyzed genetic variations associated with adipokines and various lung conditions such as interstitial lung disease, chronic obstructive pulmonary disease, asthma, lung cancer, sleep apnea, pneumonia, and tuberculosis, using data from public genome-wide studies. We employed Mendelian randomization techniques, including inverse variance weighting, weighted median, and MR-Egger regression methods, and conducted sensitivity checks to validate our findings.
RESULTS
A study using the FinnGen database, which included 198,955 participants, identified 13 SNPs associated with adiponectin. Notably, adiponectin was found to significantly reduce the risk of interstitial lung disease and idiopathic pulmonary fibrosis. However, little evidence was found to establish a direct cause-effect relationship between the six adipokines and several other lung conditions, including sarcoidosis, asthma, chronic obstructive pulmonary disease, lung cancer, tuberculosis, pneumonia, and sleep apnea syndrome.
CONCLUSION
This study reveals a reverse link between adiponectin levels and the likelihood of interstitial lung disease, including idiopathic pulmonary fibrosis.
Topics: Humans; Adipokines; Adiponectin; Mendelian Randomization Analysis; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Asthma; Idiopathic Pulmonary Fibrosis; Sleep Apnea Syndromes; Pneumonia; Tuberculosis
PubMed: 38263093
DOI: 10.1186/s12890-024-02863-8 -
International Journal of Molecular... Aug 2023Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and... (Review)
Review
Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and metabolism. It has been increasingly recognized that FABP4 dysfunction is associated with various metabolic syndromes, including obesity, diabetes, cardiovascular diseases, and metabolic inflammation. However, its explicit roles within the context of women's reproduction and pregnancy remain to be investigated. In this review, we collate recent studies probing the influence of FABP4 on female reproduction, pregnancy, and even fetal health. Elevated circulating FABP4 levels have been found to correlate with impaired reproductive function in women, such as polycystic ovary syndrome and endometriosis. Throughout pregnancy, FABP4 affects maternal-fetal interface homeostasis by affecting both glycolipid metabolism and immune tolerance, leading to adverse pregnancy outcomes, including miscarriage, gestational obesity, gestational diabetes, and preeclampsia. Moreover, maternal FABP4 levels exhibit a substantial linkage with the metabolic health of offspring. Herein, we discuss the emerging significance and potential application of FABP4 in reproduction and pregnancy health and delve into its underlying mechanism at molecular levels.
Topics: Pregnancy; Child; Humans; Female; Child Health; Abortion, Spontaneous; Adipokines; Cardiovascular Diseases; Fatty Acid-Binding Proteins
PubMed: 37628833
DOI: 10.3390/ijms241612655