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Problemy Endokrinologii Oct 2021Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to... (Review)
Review
Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.
Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; COVID-19; Humans
PubMed: 35018766
DOI: 10.14341/probl12827 -
International Journal of Molecular... Aug 2019Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are... (Review)
Review
Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.
Topics: Adipokines; Animals; Arthritis, Rheumatoid; Biomarkers; Disease Susceptibility; Gene Expression Regulation; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Resistin; Signal Transduction; T-Lymphocyte Subsets
PubMed: 31443349
DOI: 10.3390/ijms20174091 -
Physiological Research Jul 2023Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very... (Review)
Review
Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very popular and widely used. LSG leads to weight loss and metabolic improvement and also changes adipokine levels, although it is just a restrictive operation. We describe changes in pro-inflammatory (leptin, resistin, visfatin and chemerin) and anti-inflammatory adipokines (adiponectin, omentin), with adiponectin and leptin being most studied. Their levels are markedly changed after LSG and this may partially explain the weight loss seen after LSG. Adipokines are closely connected to insulin resistance and chronic inflammation both being positively influenced after LSG. Leptin regulates amount of body fat, appetite, thermogenesis and metabolic rate and its levels are positively correlated with both weight and BMI changes after operation. Resistin influences insulin sensitivity, modulates body cholesterol trafficking and its changes after operation correlate with BMI, waist circumference, fat mass, LDL cholesterol and C-reactive protein. Chemerin, an important component of immune system, decreases after bariatric surgery and its levels correlate with BMI, triglyceride levels, and blood glucose. On the other hand, pro-inflammatory adipokine adiponectin, which influences fatty acid oxidation, browning of fat tissue and energy metabolism, is declining after LSG. This decline explains improvement of glucose status after bariatric surgery in patients with diabetes and is correlated with BMI loss, waist circumference and LDL cholesterol level. Effect of LSG goes beyond calory restriction and the changes of adipokines have a great impact on health status of the bariatric patients.
Topics: Humans; Adipokines; Leptin; Resistin; Adiponectin; Cholesterol, LDL; Insulin Resistance; Laparoscopy; Gastrectomy; Weight Loss; Obesity, Morbid
PubMed: 37565420
DOI: 10.33549/physiolres.935053 -
Cancer Epidemiology, Biomarkers &... Oct 2023Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the...
BACKGROUND
Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.
METHODS
Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).
RESULTS
Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002).
CONCLUSIONS
High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.
IMPACT
Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
Topics: Male; Humans; Female; Leptin; Adiponectin; Adipokines; Receptors, Adiponectin; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Receptors, Leptin
PubMed: 37555827
DOI: 10.1158/1055-9965.EPI-23-0505 -
PeerJ 2023Cisplatin has been widely studied and found to be a highly effective anti-tumor drug. It has several side effects, including acute kidney injury (AKI). Cisplatin-induced...
Cisplatin has been widely studied and found to be a highly effective anti-tumor drug. It has several side effects, including acute kidney injury (AKI). Cisplatin-induced AKI can be primarily attributed to oxidative stress, inflammation, and apoptosis. The CTRP3 adipokine is a new adipokine that exhibits antioxidant, anti-inflammatory, and antiapoptotic properties. Despite this, the role of CTRP3 in AKI remain unclear. In cisplatin-induced AKI models, our findings demonstrated that CTRP3 expression was decreased in human proximal tubule epithelial cells (HK-2). In the experiments, HK-2 cells were first transfected with an overexpression plasmid of CTRP3 (pcDNA-CTRP3) or a small interfering RNA for CTRP3 (si-CTRP3) and induced by cisplatin; and cell oxidative stress, inflammation, proliferation, and apoptosis were found to be present. Overexpressing CTRP3 inhibited oxidative stress through decreasing malondialdehyde (MDA) levels and increasing the activity of SOD and CAT. The mRNA levels of SOD1 and SOD2 were increased in response to CTRP3 overexpression. Additionally, CTRP3 decreased TNF- and MCP-1 levels. Moreover, CTRP3 overexpression increased cisplatin-induced cell activity and decreased cell apoptosis, as indicated by the elevated numbers of EdU positive cells and decreased numbers of apoptotic cells. Consistent with these results, the overexpression of CTRP3 effectively elevated the mRNA levels of Bcl-2 and reduced the mRNA levels of Bax. In contrast, inhibition of CTRP3 expression by si-CTRP3 reversed the cisplatin-induced indices. Mechanistically, we found that the overexpression of CTRP3 can increase expression of Nrf2 and inhibit the activation of MAPK phosphorylation (ERK, JNK, and p38). Furthermore, inhibition of ERK, JNK and p38 activity eliminated aggravation of cisplatin-induced inflammation and apoptosis caused by CTRP3 knockdown. Additionally, the cisplatin-induced oxidative stress and activation of MAPK phosphorylation (ERK, JNK, and p38) in HK-2 cells were reversed by Nrf2 suppression by siRNA. Collectively, these results indicated that CTRP3 may identify as a novel target for AKI treatment and protect against cisplatin-induced AKI through the Nrf2/MAPK pathway.
Topics: Humans; Acute Kidney Injury; Adipokines; Cell Death; Cisplatin; Inflammation; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 37637169
DOI: 10.7717/peerj.15890 -
Current Pharmaceutical Design 2017Adipokines are bioactive proteins that mediate proliferation, metabolism, inflammation, and angiogenesis. Adiponectin is an important adipokine that exerts multiple key... (Review)
Review
Adipokines are bioactive proteins that mediate proliferation, metabolism, inflammation, and angiogenesis. Adiponectin is an important adipokine that exerts multiple key functions via its anti-metabolic syndrome and anti-inflammatory properties. A number of adiponectin receptors, AdipoR1, AdipoR2 and T-cadherin, have been identified. Recent studies have suggested the involvement of adiponectin and receptors in several cancers, including prostate, breast, endometrial, brain, and colon cancer. Altered levels of adiponectin expression, or its interacting receptors, in cancers can lead to dysregulation of signaling pathways. Our current review describes the molecular mechanisms underlying the anti-tumorigenesis activity of adiponectin and the role of its receptors in prostate carcinogenesis, and provides perspectives of adiponectin-mediated signaling as a potential target for therapy.
Topics: Adipokines; Adiponectin; Animals; Humans; Male; Molecular Targeted Therapy; Prostatic Neoplasms; Receptors, Adiponectin; Signal Transduction
PubMed: 28183249
DOI: 10.2174/1381612823666170208123553 -
Obesity Reviews : An Official Journal... Sep 2016Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve... (Review)
Review
Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.
Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Bariatric Surgery; Catecholamines; Disease Models, Animal; Humans; Inflammation; Insulin; Insulin Resistance; Obesity
PubMed: 27272117
DOI: 10.1111/obr.12429 -
International Journal of Molecular... Apr 2017Overweight is believed to be associated with colorectal cancer risk. Adipose tissue is loose connective tissue composed of adipocytes. It is now recognized as a major... (Review)
Review
Overweight is believed to be associated with colorectal cancer risk. Adipose tissue is loose connective tissue composed of adipocytes. It is now recognized as a major endocrine organ, secreting humoral factors collectively called adipokines. Aberrant hormonal systems consisting of modulated adipokines and their receptors are thought to play a role in colorectal carcinogenesis and cancer progression in obese conditions. However, it is still unclear whether and how each adipokine relates to colorectal carcinogenesis. Notably, a couple of molecules that were initially proposed to be obesity-related adipokines were disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1 (also known as omentin-1), whose levels are decreased in obesity, act as tumor suppressor factors in various cancers. Numerous studies have demonstrated a link between the insufficient expression and function of adiponectin and its receptor, T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated that loss of TMEM207, which is critical for the proper processing of intelectin-1 in the colon mucosa, leads to insufficient intelectin-1 production, thus participating in colorectal carcinogenesis. Here, we discuss the recent understanding of the role of adipokines in colorectal carcinogenesis and subsequently describe the potent tumor suppressor roles of intelectin-1 and TMEM207 in colorectal cancer.
Topics: Adipokines; Adiponectin; Animals; Carrier Proteins; Cell Transformation, Neoplastic; Colorectal Neoplasms; Cytokines; GPI-Linked Proteins; Humans; Lectins; Leptin; Membrane Proteins; Obesity; Overweight; Receptors, Adipokine
PubMed: 28422056
DOI: 10.3390/ijms18040866 -
International Journal of Molecular... May 2022The current obesity pandemic has been expanding in both developing and developed countries. This suggests that the factors contributing to this condition need to be... (Review)
Review
The current obesity pandemic has been expanding in both developing and developed countries. This suggests that the factors contributing to this condition need to be reconsidered since some new factors are arising as etiological causes of this disease. Moreover, recent clinical and experimental findings have shown an association between the progress of obesity and some infections, and the functions of adipose tissues, which involve cell metabolism and adipokine release, among others. Furthermore, it has recently been reported that adipocytes could either be reservoirs for these pathogens or play an active role in this process. In addition, there is abundant evidence indicating that during obesity, the immune system is exacerbated, suggesting an increased susceptibility of the patient to the development of several forms of illness or death. Thus, there could be a relationship between infection as a trigger for an increase in adipose cells and the impact on the metabolism that contributes to the development of obesity. In this review, we describe the findings concerning the role of adipose tissue as a mediator in the immune response as well as the possible role of adipocytes as infection targets, with both roles constituting a possible cause of obesity.
Topics: Adipocytes; Adipokines; Adipose Tissue; Humans; Immunity; Obesity
PubMed: 35682832
DOI: 10.3390/ijms23116154 -
International Journal of Molecular... Jul 2022Obesity is a chronic disease caused by an excess of adipose tissue that may impair health by altering the functionality of various organs, including the lungs. Excessive... (Review)
Review
Obesity is a chronic disease caused by an excess of adipose tissue that may impair health by altering the functionality of various organs, including the lungs. Excessive deposition of fat in the abdominal area can lead to abnormal positioning of the diaphragm and consequent reduction in lung volume, leading to a heightened demand for ventilation and increased exposure to respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and obstructive sleep apnoea. In addition to mechanical ventilatory constraints, excess fat and ectopic deposition in visceral depots can lead to adipose tissue dysfunction, which promotes metabolic disorders. An altered adipokine-secretion profile from dysfunctional adipose tissue in morbid obesity fosters systemic, low-grade inflammation, impairing pulmonary immune response and promoting airway hyperresponsiveness. A potential target of these adipokines could be the NLRP3 inflammasome, a critical component of the innate immune system, the harmful pro-inflammatory effect of which affects both adipose and lung tissue in obesity. In this review, we will investigate the crosstalk between adipose tissue and the lung in obesity, highlighting the main inflammatory mediators and novel therapeutic targets in preventing pulmonary dysfunction.
Topics: Adipokines; Adipose Tissue; Humans; Inflammasomes; Inflammation; Obesity, Morbid
PubMed: 35806353
DOI: 10.3390/ijms23137349