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Frontiers in Endocrinology 2022Hormone-dependent cancers are a major cause of morbidity and mortality in both genders. Accumulating evidence suggest that adiponectin, an adipokine with multifaceted... (Review)
Review
Hormone-dependent cancers are a major cause of morbidity and mortality in both genders. Accumulating evidence suggest that adiponectin, an adipokine with multifaceted functions, is implicated in the pathogenesis of several malignancies. In the present review, we discuss the existing data regarding this relationship. Several observational studies showed that low adiponectin levels are associated with higher risk for breast, cervical, endometrial, ovarian and prostate cancer. A relationship between adiponectin and the aggressiveness of some of these tumors has also been reported. studies reported that adiponectin inhibits the proliferation and induces apoptosis of breast, cervical, endometrial, ovarian and prostate cancer cells. Given the high prevalence of these cancers and the substantial associated morbidity and mortality, the role of agents that increase adiponectin levels and/or stimulate its activity should be evaluated for the prevention and management of these common tumors.
Topics: Female; Humans; Male; Adiponectin; Receptors, Adiponectin; Ovarian Neoplasms; Prostatic Neoplasms; Adipokines
PubMed: 36277714
DOI: 10.3389/fendo.2022.1018515 -
ELife Apr 2021Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of...
Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet. In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.
Topics: Adiponectin; Aging; Animals; Female; Glucose; Homeostasis; Insulin Resistance; Lipid Metabolism; Longevity; Male; Mice; Mice, Transgenic
PubMed: 33904399
DOI: 10.7554/eLife.65108 -
Nature Cell Biology May 2022How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not...
How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not required for HSC function or haematopoiesis, promotes stem/progenitor cell proliferation after bacterial infection and myeloablation. Adiponectin binds two receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin binding. Here we found that adiponectin receptors are non-cell-autonomously required in haematopoietic cells to promote HSC quiescence and self-renewal. Adiponectin receptor signalling suppresses inflammatory cytokine expression by myeloid cells and T cells, including interferon-γ and tumour necrosis factor. Without adiponectin receptors, the levels of these factors increase, chronically activating HSCs, reducing their self-renewal potential and depleting them during ageing. Pathogen infection accelerates this loss of HSC self-renewal potential. Blocking interferon-γ or tumour necrosis factor signalling partially rescues these effects. Adiponectin receptors are thus required in immune cells to sustain HSC quiescence and to prevent premature HSC depletion by reducing inflammation.
Topics: Adiponectin; Adult; Hematopoietic Stem Cells; Humans; Inflammation; Interferon-gamma; Receptors, Adiponectin; Tumor Necrosis Factors
PubMed: 35513711
DOI: 10.1038/s41556-022-00909-9 -
International Journal of Molecular... Jun 2019Adiponectin, the most abundant secreted adipokine, has received great attention from the scientific community since its discovery [...].
Adiponectin, the most abundant secreted adipokine, has received great attention from the scientific community since its discovery [...].
Topics: Adiponectin; Animals; Humans; Metabolic Diseases; Signal Transduction
PubMed: 31200595
DOI: 10.3390/ijms20122894 -
Lipids in Health and Disease Aug 2021Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by abnormal T cell activation and excessive proliferation of keratinocytes. In addition... (Review)
Review
Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by abnormal T cell activation and excessive proliferation of keratinocytes. In addition to skin manifestations, psoriasis has been associated with multiple metabolic comorbidities, such as obesity, insulin resistance, and diabetes. An increasing amount of evidence has highlighted the core role of adipokines in adipose tissue and the immune system. This review focus on the role of adiponectin in the pathophysiology of psoriasis and its comorbidities, highlighting the future research avenues.
Topics: Adiponectin; Humans; Psoriasis
PubMed: 34372872
DOI: 10.1186/s12944-021-01510-z -
International Journal of Molecular... Oct 2017A functional relationship is suggested between two well-known protein hormones, insulin-like growth factor 1 (IGF-1) and adiponectin. In the last two decades in fact,... (Review)
Review
A functional relationship is suggested between two well-known protein hormones, insulin-like growth factor 1 (IGF-1) and adiponectin. In the last two decades in fact, different experimental evidence has indicated a non-random link between them. Here, we describe briefly the IGF-1 and adiponectin systems, and we then focus on their putative interplay in relation to several pathological conditions, including obesity, diabetes, insulin resistance, cardiovascular disease, and cancer. Although the existing studies are hardly comparable, they definitely indicate a functional connection between these two protein hormones. In conclusion, the current knowledge strongly encourages further research into the common, as well as novel, mechanisms through which IGF-1 and adiponectin exert their concerted action.
Topics: Adiponectin; Animals; Cardiovascular Diseases; Diabetes Mellitus; Disease Susceptibility; Gene Expression Regulation; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Neoplasms; Obesity; Protein Binding; Signal Transduction
PubMed: 29036907
DOI: 10.3390/ijms18102145 -
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 -
Cells Oct 2023Adiponectin (adipoq), the most abundant hormone in circulation, has many beneficial effects on the cardiovascular system, in part by preserving the contractile phenotype...
Adiponectin (adipoq), the most abundant hormone in circulation, has many beneficial effects on the cardiovascular system, in part by preserving the contractile phenotype of vascular smooth muscle cells (VSMCs). However, the lack of adiponectin or its receptor and treatment with recombinant adiponectin have shown contradictory effects on plaque in mice. RNA sequence of and VSMCs from male aortas identified a critical role for adiponectin in AKT signaling, the extracellular matrix (ECM), and TGF-β signaling. Upregulation of AKT activity mediated proliferation and migration of cells. Activation of AMPK with metformin or AdipoRon reduced AKT-dependent proliferation and migration of cells but did not improve the expression of contractile genes. Adiponectin deficiency impaired oxidative phosphorylation (OXPHOS), increased expression of glycolytic enzymes, and elevated mitochondrial reactive oxygen species (ROS) (superoxide, and hydrogen peroxide). Anti-atherogenic mechanisms targeted the ECM in cells, downregulating MMP2 and 9 and upregulating decorin (DCN) and elastin (ELN). In vivo, the main sex differences in protein expression in aortas involved a more robust upregulation of MMP3 in females than males. Females also showed a reduction in DCN, which was not affected in males. Our study uncovered the AKT/MAPK/TGF-β network as a central regulator of VSMC phenotype.
Topics: Male; Mice; Female; Animals; Adiponectin; Proto-Oncogene Proteins c-akt; Muscle, Smooth, Vascular; Phenotype; Transforming Growth Factor beta
PubMed: 37887338
DOI: 10.3390/cells12202493 -
International Journal of Molecular... Apr 2022Gestational diabetes mellitus (GDM) has become a major public health problem and one of the most discussed issues in modern obstetrics. GDM is associated with serious... (Review)
Review
Gestational diabetes mellitus (GDM) has become a major public health problem and one of the most discussed issues in modern obstetrics. GDM is associated with serious adverse perinatal outcomes and long-term health consequences for both the mother and child. Currently, the importance and purposefulness of finding a biopredictor that will enable the identification of women with an increased risk of developing GDM as early as the beginning of pregnancy are highly emphasized. Both "older" molecules, such as adiponectin and leptin, and "newer" adipokines, including fatty acid-binding protein 4 (FABP4), have proven to be of pathophysiological importance in GDM. Therefore, in our previous review, we presented 13 novel biomolecules, i.e., galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, FABP4, fibroblast growth factor 21, and lipocalin-2. The purpose of this review is to present the potential and importance of another nine lesser known molecules in the pathogenesis of GDM, i.e., 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), angiopoietin-like protein-8 (ANGPTL-8), nesfatin-1, afamin, adropin, fetuin-A, zonulin, secreted frizzled-related proteins (), and amylin. It seems that two of them, fetuin-A and zonulin in high serum levels, may be applied as biopredictors of GDM.
Topics: Adipokines; Adiponectin; Diabetes, Gestational; Female; Humans; Pregnancy; alpha-2-HS-Glycoprotein
PubMed: 35457182
DOI: 10.3390/ijms23084364 -
Molecular Metabolism Dec 2023The disease progression of the metabolic syndrome is associated with prolonged hyperlipidemia and insulin resistance, eventually giving rise to impaired insulin...
The disease progression of the metabolic syndrome is associated with prolonged hyperlipidemia and insulin resistance, eventually giving rise to impaired insulin secretion, often concomitant with hypoadiponectinemia. As an adipose tissue derived hormone, adiponectin is beneficial for insulin secretion and β cell health and differentiation. However, the down-stream pathway of adiponectin in the pancreatic islets has not been studied extensively. Here, along with the overall reduction of endocrine pancreatic function in islets from adiponectin KO mice, we examine PPARα and HNF4α as additional down-regulated transcription factors during a prolonged metabolic challenge. To elucidate the function of β cell-specific PPARα and HNF4α expression, we developed doxycycline inducible pancreatic β cell-specific PPARα (β-PPARα) and HNF4α (β-HNF4α) overexpression mice. β-PPARα mice exhibited improved protection from lipotoxicity, but elevated β-oxidative damage in the islets, and also displayed lowered phospholipid levels and impaired glucose-stimulated insulin secretion. β-HNF4α mice showed a more severe phenotype when compared to β-PPARα mice, characterized by lower body weight, small islet mass and impaired insulin secretion. RNA-sequencing of the islets of these models highlights overlapping yet unique roles of β-PPARα and β-HNF4α. Given that β-HNF4α potently induces PPARα expression, we define a novel adiponectin-HNF4α-PPARα cascade. We further analyzed downstream genes consistently regulated by this axis. Among them, the islet amyloid polypeptide (IAPP) gene is an important target and accumulates in adiponectin KO mice. We propose a new mechanism of IAPP aggregation in type 2 diabetes through reduced adiponectin action.
Topics: Animals; Mice; Adiponectin; Diabetes Mellitus, Type 2; Insulin; Insulin-Secreting Cells; PPAR alpha
PubMed: 37806486
DOI: 10.1016/j.molmet.2023.101821