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Circulation Research Jan 2021The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of... (Review)
Review
The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of investigating adipose-mediated tissue crosstalk. Both obesity-associated hyperleptinemia and hypoadiponectinemia are important biomarkers to predict cardiovascular outcomes, suggesting a crucial role for adiponectin and leptin in obesity-associated cardiovascular disorders. Normal physiological levels of adiponectin and leptin are indeed essential to maintain proper cardiovascular function. Insufficient adiponectin and leptin signaling results in cardiovascular dysfunction. However, a paradox of high levels of both leptin and adiponectin is emerging in the pathogenesis of cardiovascular disorders. Here, we (1) summarize the recent progress in the field of adiponectin and leptin and its association with cardiovascular disorders, (2) further discuss the underlying mechanisms for this new paradox of leptin and adiponectin action, and (3) explore the possible application of partial leptin reduction, in addition to increasing the adiponectin/leptin ratio as a means to prevent or reverse cardiovascular disorders.
Topics: Adiponectin; Adipose Tissue; Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Leptin; Metabolism, Inborn Errors; Obesity; Signal Transduction
PubMed: 33411633
DOI: 10.1161/CIRCRESAHA.120.314458 -
Clinical Science (London, England :... Apr 2020Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life.... (Review)
Review
Maternal obesity is associated with pregnancy complications and increases the risk for the infant to develop obesity, diabetes and cardiovascular disease later in life. However, the mechanisms linking the maternal obesogenic environment to adverse short- and long-term outcomes remain poorly understood. As compared with pregnant women with normal BMI, women entering pregnancy obese have more pronounced insulin resistance, higher circulating plasma insulin, leptin, IGF-1, lipids and possibly proinflammatory cytokines and lower plasma adiponectin. Importantly, the changes in maternal levels of nutrients, growth factors and hormones in maternal obesity modulate placental function. For example, high insulin, leptin, IGF-1 and low adiponectin in obese pregnant women activate mTOR signaling in the placenta, promoting protein synthesis, mitochondrial function and nutrient transport. These changes are believed to increase fetal nutrient supply and contribute to fetal overgrowth and/or adiposity in offspring, which increases the risk to develop disease later in life. However, the majority of obese women give birth to normal weight infants and these pregnancies are also associated with activation of inflammatory signaling pathways, oxidative stress, decreased oxidative phosphorylation and lipid accumulation in the placenta. Recent bioinformatics approaches have expanded our understanding of how maternal obesity affects the placenta; however, the link between changes in placental function and adverse outcomes in obese women giving birth to normal sized infants is unclear. Interventions that specifically target placental function, such as activation of placental adiponectin receptors, may prevent the transmission of metabolic disease from obese women to the next generation.
Topics: Adiponectin; Adiposity; Animals; Female; Humans; Insulin-Like Growth Factor I; Obesity, Maternal; Placenta; Pregnancy; Pregnancy Complications
PubMed: 32313958
DOI: 10.1042/CS20190266 -
Cellular and Molecular Life Sciences :... May 2022Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and... (Review)
Review
Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.
Topics: Adipokines; Adiponectin; Adiposity; Atherosclerosis; Cardiovascular Diseases; Humans; Interleukin-6; Leptin; Obesity
PubMed: 35503385
DOI: 10.1007/s00018-022-04286-2 -
International Journal of Molecular... Feb 2020Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular,... (Review)
Review
Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.
Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Adipose Tissue, White; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Atherosclerosis; Autoimmune Diseases; Diabetes Mellitus, Type 2; Disease; Humans; Inflammation; Inflammatory Bowel Diseases; Obesity; Protein Isoforms; Renal Insufficiency, Chronic
PubMed: 32059381
DOI: 10.3390/ijms21041219 -
Journal of Lipid Research Oct 2019The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more... (Review)
Review
The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more adipose tissue-secreted signaling mediators (adipokines) have been identified since then, and much has been learned about how adipose tissue communicates with other organs of the body to maintain systemic homeostasis. Beyond proteins, additional factors, such as lipids, metabolites, noncoding RNAs, and extracellular vesicles (EVs), released by adipose tissue participate in this process. Here, we review the diverse signaling mediators and mechanisms adipose tissue utilizes to relay information to other organs. We discuss recently identified adipokines (proteins, lipids, and metabolites) and briefly outline the contributions of noncoding RNAs and EVs to the ever-increasing complexities of adipose tissue inter-organ communication. We conclude by reflecting on central aspects of adipokine biology, namely, the contribution of distinct adipose tissue depots and cell types to adipokine secretion, the phenomenon of adipokine resistance, and the capacity of adipose tissue to act both as a source and sink of signaling mediators.
Topics: Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Lipid Metabolism; Signal Transduction
PubMed: 31209153
DOI: 10.1194/jlr.R094060 -
The Journal of Clinical Investigation Oct 2019Adipose tissue plays important roles in regulating whole-body energy metabolism through its storage function in white adipocytes and its dissipating function in brown... (Review)
Review
Adipose tissue plays important roles in regulating whole-body energy metabolism through its storage function in white adipocytes and its dissipating function in brown and beige adipocytes. Adipose tissue also produces a variety of secreted factors called adipocytokines, including leptin and adiponectin. Furthermore, recent studies have suggested the important roles of extracellular vesicles of endosomal origin termed exosomes, which are secreted from adipocytes and other cells in adipose tissue and influence whole-body glucose and lipid metabolism. Adiponectin is known to be a pleiotropic organ-protective protein that is exclusively produced by adipocytes and decreased in obesity. Adiponectin accumulates in tissues such as heart, muscle, and vascular endothelium through binding with T-cadherin, a glycosylphosphatidylinositol-anchored (GPI-anchored) cadherin. Recently, adiponectin was found to enhance exosome biogenesis and secretion, leading to a decrease in cellular ceramides, excess of which is known to cause insulin resistance and cardiovascular disease phenotypes. These findings support the hypothesis that adipose tissue metabolism systemically regulates exosome production and whole-body metabolism through exosomes. This review focuses on intra-adipose and interorgan communication by exosomes, adiponectin-stimulated exosome production, and their dysregulation in metabolic diseases.
Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Cadherins; Exosomes; Glucose; Humans; Lipid Metabolism; Metabolic Syndrome; Signal Transduction
PubMed: 31483293
DOI: 10.1172/JCI129193 -
Nutrients Apr 2021Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine).... (Review)
Review
Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine). Available evidence suggests that adiponectin is involved in a variety of physiological functions, molecular and cellular events, including lipid metabolism, energy regulation, immune response and inflammation, and insulin sensitivity. It has a protective effect on neurons and neural stem cells. Adiponectin levels have been reported to be negatively correlated with cancer, cardiovascular disease, and diabetes, and shown to be affected (i.e., significantly increased) by proper healthy nutrition. The present review comprehensively overviews the role of adiponectin in a range of diseases, showing that it can be used as a biomarker for diagnosing these disorders as well as a target for monitoring the effectiveness of preventive and treatment interventions.
Topics: Adiponectin; Adipose Tissue; Alzheimer Disease; Animals; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Energy Metabolism; Humans; Immunity; Inflammation; Insulin Resistance; Lipid Metabolism; Neoplasms; Nutritional Status; Protective Factors
PubMed: 33918360
DOI: 10.3390/nu13041180 -
Journal of Experimental & Clinical... Jan 2022Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying...
BACKGROUND
Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions. However, the biological actions of adiponectin in cancer-specific lipid metabolism and its role in the regulation of cancer cell growth remain elusive.
METHODS
The effects of adiponectin on fatty acid metabolism were evaluated by measuring the cellular neutral lipid pool, free fatty acid level, and fatty acid oxidation (FAO). Colocalization between fluorescent-labeled lipid droplets and LC3/lysosomes was employed to detect lipophagy activation. Cell viability and apoptosis were examined by MTS assay, caspase-3/7 activity measurement, TUNEL assay, and Annexin V binding assay. Gene expression was determined by real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The transcriptional activity of SREBP-1 was examined by a specific dsDNA binding assay. The modulatory roles of SIRT-1 and adiponectin-activated mediators were confirmed by gene silencing and/or using their pharmacological inhibitors. Observations from in vitro assays were further validated in an MDA-MB-231 orthotopic breast tumor model.
RESULTS
Globular adiponectin (gAcrp) prominently decreased the cellular lipid pool in different breast cancer cells. The cellular lipid deficiency promoted apoptosis by causing disruption of lipid rafts and blocking raft-associated signal transduction. Mechanistically, dysregulated cellular lipid homeostasis by adiponectin was induced by two concerted actions: 1) suppression of fatty acid synthesis (FAS) through downregulation of SREBP-1 and FAS-related enzymes, and 2) stimulation of lipophagy-mediated lipolysis and FAO. Notably, SIRT-1 induction critically contributed to the adiponectin-induced metabolic alterations. Finally, fatty acid metabolic remodeling by adiponectin and the key role of SIRT-1 were confirmed in nude mice bearing breast tumor xenografts.
CONCLUSION
This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.
Topics: Adiponectin; Animals; Breast Neoplasms; Cell Death; Fatty Acids; Female; Humans; Mice; Mice, Nude; Transfection
PubMed: 34986886
DOI: 10.1186/s13046-021-02223-y -
Cell Stem Cell Nov 2022A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We...
A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We found that SSCs in adult bone marrow can be identified based on Lepr and Adiponectin-cre/creER expression while SSCs in adult periosteum can be identified based on Gli1 expression. Under steady-state conditions, new bone arose primarily from bone marrow SSCs. After bone injuries, both SSC populations began proliferating but made very different contributions to bone repair. Drill injuries were primarily repaired by LepR/Adiponectin bone marrow SSCs. Conversely, bicortical fractures were primarily repaired by Gli1 periosteal SSCs, though LepR/Adiponectin bone marrow cells transiently formed trabecular bone at the fracture site. Gli1 periosteal cells also regenerated LepR bone marrow stromal cells that expressed hematopoietic niche factors at fracture sites. Different bone injuries are thus repaired by different SSCs, with periosteal cells regenerating bone and marrow stroma after non-stabilized fractures.
Topics: Humans; Adult; Bone Marrow; Zinc Finger Protein GLI1; Adiponectin; Stem Cells; Periosteum; Bone Marrow Cells
PubMed: 36272401
DOI: 10.1016/j.stem.2022.10.002 -
Investigative Ophthalmology & Visual... Mar 2023Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This...
PURPOSE
Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This study aimed to clarify this uncertainty by evaluating the link between multiple glycemic traits and myopia.
METHODS
We employed a two-sample Mendelian randomization (MR) design using summary statistics from independent genome-wide association studies. A total of six glycemic traits, including adiponectin, body mass index, fasting blood glucose, fasting insulin, hemoglobin A1c (HbA1c), and proinsulin levels, were used as exposures, and myopia was used as the outcome. The inverse-variance-weighted (IVW) method was the main applied analytic tool and was complemented with comprehensive sensitivity analyses.
RESULTS
Out of the six glycemic traits studied, we found that adiponectin was significantly associated with myopia. The genetically predicted level of adiponectin was consistently negatively associated with myopia incidence: IVW (odds ratio [OR] = 0.990; P = 2.66 × 10-3), MR Egger (OR = 0.983; P = 3.47 × 10-3), weighted median method (OR = 0.989; P = 0.01), and weighted mode method (OR = 0.987; P = 0.01). Evidence from all sensitivity analyses further supported these associations. In addition, a higher HbA1c level was associated with a greater risk of myopia: IVW (OR = 1.022; P = 3.06 × 10-5).
CONCLUSIONS
Genetic evidence shows that low adiponectin levels and high HbA1c are associated with an increased risk of myopia. Given that physical activity and sugar intake are controllable variables in blood glycemia treatment, these findings provide new insights into potential strategies to delay myopia onset.
Topics: Humans; Adiponectin; Genome-Wide Association Study; Glycated Hemoglobin; Myopia; Sugars
PubMed: 36867130
DOI: 10.1167/iovs.64.3.7