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Progress in Lipid Research Jul 2023Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone.... (Review)
Review
Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone. Asprosin also stimulates appetite and regulates glucose and lipid metabolism. Its identified receptors so far include Olfr734 and Ptprd. Clinical studies have found that asprosin may be associated with cardiometabolic diseases. Asprosin may have diagnostic and therapeutic potential in obesity, diabetes, metabolic syndrome and atherosclerotic cardiovascular diseases. Herein, the structure, receptors, and functions of asprosin and its relationship with cardiometabolic diseases are summarized based on recent findings.
Topics: Humans; Adipokines; Cardiovascular Diseases; Peptide Hormones; Microfilament Proteins; Peptide Fragments; Fibrillin-1; Glucose
PubMed: 37473965
DOI: 10.1016/j.plipres.2023.101240 -
Nature Reviews. Endocrinology Dec 2023Adipose tissue is an endocrine organ and a crucial regulator of energy storage and systemic metabolic homeostasis. Additionally, adipose tissue is a pivotal regulator of... (Review)
Review
Adipose tissue is an endocrine organ and a crucial regulator of energy storage and systemic metabolic homeostasis. Additionally, adipose tissue is a pivotal regulator of cardiovascular health and disease, mediated in part by the endocrine and paracrine secretion of several bioactive products, such as adipokines. Adipose vasculature has an instrumental role in the modulation of adipose tissue expansion, homeostasis and metabolism. The role of the adipose vasculature has been extensively explored in the context of obesity, which is recognized as a global health problem. Obesity-induced accumulation of fat, in combination with vascular rarefaction, promotes adipocyte dysfunction and induces oxidative stress, hypoxia and inflammation. It is now recognized that obesity-associated endothelial dysfunction often precedes the development of cardiovascular diseases. Investigations have revealed heterogeneity within the vascular niche and dynamic reciprocity between vascular and adipose cells, which can become dysregulated in obesity. Here we provide a comprehensive overview of the evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.
Topics: Humans; Adipose Tissue; Obesity; Adipocytes; Adipokines; Biology
PubMed: 37749386
DOI: 10.1038/s41574-023-00893-6 -
Pharmacological Research Sep 2023Adaptive thermogenesis is the heat production by muscle contractions (shivering thermogenesis) or brown adipose tissue (BAT) and beige fat (non-shivering thermogenesis)... (Review)
Review
Adaptive thermogenesis is the heat production by muscle contractions (shivering thermogenesis) or brown adipose tissue (BAT) and beige fat (non-shivering thermogenesis) in response to external stimuli, including cold exposure. BAT and beige fat communicate with peripheral organs and the brain through a variegate secretory and absorption processes - controlling adipokines, microRNAs, extracellular vesicles, and metabolites - and have received much attention as potential therapeutic targets for managing obesity-related disorders. The sympathetic nervous system and norepinephrine-releasing adipose tissue macrophages (ATM) activate uncoupling protein 1 (UCP1), expressed explicitly in brown and beige adipocytes, dissolving the electrochemical gradient and uncoupling tricarboxylic acid cycle and the electron transport chain from ATP production. Mounting evidence has attracted attention to the multiple effects of dietary and endogenously synthesised amino acids in BAT thermogenesis and metabolic phenotype in animals and humans. However, the mechanisms implicated in these processes have yet to be conclusively characterized. In the present review article, we aim to define the principal investigation areas in this context, including intestinal microbiota constitution, adipose autophagy modulation, and secretome and metabolic fluxes control, which lead to increased brown/beige thermogenesis. Finally, also based on our recent epicardial adipose tissue results, we summarise the evidence supporting the notion that the new dual and triple agonists of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG) receptor - with never before seen weight loss and insulin-sensitizing efficacy - promote thermogenic-like amino acid profiles in BAT with robust heat production and likely trigger sympathetic activation and adaptive thermogenesis by controlling amino acid metabolism and ATM expansion in BAT and beige fat.
Topics: Animals; Humans; Amino Acids; Thermogenesis; Metabolic Diseases; Adipose Tissue, Brown; Adipokines
PubMed: 37619907
DOI: 10.1016/j.phrs.2023.106892 -
Molecular Metabolism Dec 2023Tissue crosstalk mediated by secreted hormones underlies the integrative control of metabolism. We previously showed that CTRP13/C1QL3, a secreted protein of the C1q...
OBJECTIVE
Tissue crosstalk mediated by secreted hormones underlies the integrative control of metabolism. We previously showed that CTRP13/C1QL3, a secreted protein of the C1q family, can improve glucose metabolism and insulin action in vitro and reduce food intake and body weight in mice when centrally delivered. A role for CTRP13 in regulating insulin secretion in isolated islets has also been demonstrated. It remains unclear, however, whether the effects of CTRP13 on cultured cells and in mice reflect the physiological function of the protein. Here, we use a loss-of-function mouse model to address whether CTRP13 is required for metabolic homeostasis.
METHODS
WT and Ctrp13 knockout (KO) mice fed a standard chow or a high-fat diet were subjected to comprehensive metabolic phenotyping. Transcriptomic analyses were carried out on visceral and subcutaneous fat, liver, and skeletal muscle to identify pathways altered by CTRP13 deficiency. RNA-seq data was further integrated with the Metabolic Syndrome in Man (METSIM) cohort data. Adjusted regression analysis was used to demonstrate that genetic variation of CTRP13 expression accounts for a significant proportion of variance between differentially expressed genes (DEGs) in adipose tissue and metabolic traits in humans.
RESULTS
Contrary to expectation, chow-fed Ctrp13-KO male mice had elevated physical activity, lower body weight, and improved lipid handling. On a high-fat diet (HFD), Ctrp13-KO mice of either sex were consistently more active and leaner. Loss of CTRP13 reduced hepatic glucose output and improved glucose tolerance, insulin sensitivity, and triglyceride clearance, though with notable sex differences. Consistent with the lean phenotype, transcriptomic analyses revealed a lower inflammatory profile in visceral fat and liver. Reduced hepatic steatosis was correlated with the suppression of lipid synthesis and enhanced lipid catabolism gene expression. Visceral fat had the largest number of DEGs and mediation analyses on the human orthologs of the DEGs suggested the potential causal contribution of CTRP13 to human metabolic syndrome.
CONCLUSIONS
Our results suggest that CTRP13 is a negative metabolic regulator, and its deficiency improves systemic metabolic profiles. Our data also suggest the reduction in circulating human CTRP13 levels seen in obesity and diabetes may reflect a compensatory physiologic response to counteract insulin resistance.
Topics: Animals; Female; Humans; Male; Mice; Adipokines; Body Weight; Glucose; Insulin Resistance; Lipid Metabolism; Lipids; Metabolic Syndrome
PubMed: 37844630
DOI: 10.1016/j.molmet.2023.101824 -
The Journal of Physiological Sciences :... Nov 2023Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and... (Review)
Review
Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and exerkines, such as apelin, adiponectin, leptin, irisin, and chemerin. Exercise and apelin increase thermogenesis and glucose uptake in pregnancy by activating AMPK, PI3K, PGC-1α, AKT1, UCP3, and sarcolipin. Exercise increases apelin levels to reduce preeclampsia symptoms by increasing eNOS, NO, placental growth factor (PlGF), and VEGF and decreasing levels of fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and oxidative stress. A negative relationship has been reported between plasma leptin and VOpeak/kg and VOpeak in women with gestational diabetes. In active women, decreases in leptin levels reduce the risk of preeclampsia by ~ 40%. Higher adiponectin levels are associated with greater physical activity and lead to increased insulin sensitivity. Increased adiponectin levels in preeclampsia and exercise counteract inflammatory and atherogenic activities while also having vascular protective effects. Exercise increases irisin levels that correlate negatively with fasting glucose, insulin concentration, and glycosylated hemoglobin levels. Irisin augments mRNA expression levels of UCP1 and cell death-inducing DNA fragmentation factor-like effector A (cidea) to cause browning of adipose tissue, increased thermogenesis, and increased energy consumption. Irisin concentrations in mothers with preeclampsia in the third trimester negatively correlate with systolic and diastolic blood pressure. Expression levels of chemerin, IL-6, and TNF-α are increased in gestational diabetes, and the increases in chemerin in late pregnancy positively correlate with the ratio of sFlt-1 to PlGF as a marker of preeclampsia. The effects of physical exercise on placentokines and exerkines in women at various stages of pregnancy remain poorly understood.
Topics: Pregnancy; Female; Humans; Placenta Growth Factor; Pre-Eclampsia; Pregnancy Proteins; Leptin; Apelin; Biomarkers; Diabetes, Gestational; Adiponectin; Fibronectins
PubMed: 37964253
DOI: 10.1186/s12576-023-00885-1 -
Molecular Biology Reports Jul 2023Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In... (Review)
Review
Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In addition, obesity has been associated with a poor prognosis, an increased risk of metastasis and mortality, and resistance to anti-cancer therapies. The pathophysiological mechanisms underlying the obesity-cancer connection have not yet been fully elucidated. However, this connection could result, at least in part, from the action of adipokines, whose levels are increased in obesity. Among these adipokines, evidence suggests leptin's critical role in linking obesity to cancer. In this review, we first summarize the current state of the literature regarding the implication of leptin in tumorigenic processes. Next, we focus on the effects of leptin on the anti-tumor immune response. Then, we discuss the influence of leptin on the efficiency of antineoplastic treatments and the development of tumor resistance. Finally, we highlight the use of leptin as a potential target for the prevention and treatment of cancer.
Topics: Humans; Adipokines; Antineoplastic Agents; Leptin; Neoplasms; Obesity
PubMed: 37227675
DOI: 10.1007/s11033-023-08525-y -
International Journal of Molecular... Dec 2023The rising incidence of obesity has coincided with rising levels of poor reproductive outcomes. The molecular basis for the association of infertility in obese males is... (Review)
Review
The rising incidence of obesity has coincided with rising levels of poor reproductive outcomes. The molecular basis for the association of infertility in obese males is now being explained through various mechanisms. Insulin resistance, hyperglycemia, and changes in serum and gonadal concentrations of adipokines, like leptin, adiponectin, resistin, and ghrelin have been implicated as causes of male infertility in obese males. The effects of obesity and hypogonadism form a vicious cycle whereby dysregulation of the hypothalamic-pituitary-testicular axis-due to the effect of the release of multiple mediators, thus decreasing GnRH release from the hypothalamus-causes decreases in LH and FSH levels. This leads to lower levels of testosterone, which further increases adiposity because of increased lipogenesis. Cytokines such as TNF-α and interleukins, sirtuins, and other inflammatory mediators like reactive oxygen species are known to affect fertility in obese male adults. There is evidence that parental obesity can be transferred through subsequent generations to offspring through epigenetic marks. Thus, negative expressions like obesity and infertility have been linked to epigenetic marks being altered in previous generations. The interesting aspect is that these epigenetic expressions can be reverted by removing the triggering factors. These positive modifications are also transmitted to subsequent generations.
Topics: Adult; Humans; Male; Infertility, Male; Obesity; Fertility; Adiposity; Adipokines
PubMed: 38203349
DOI: 10.3390/ijms25010179 -
Metabolism: Clinical and Experimental Nov 2023The role of metabolic/inflammatory hormonal systems in metabolic dysfunction associated steatotic liver disease (MASLD) remains to be fully elucidated. (Observational Study)
Observational Study
BACKGROUND
The role of metabolic/inflammatory hormonal systems in metabolic dysfunction associated steatotic liver disease (MASLD) remains to be fully elucidated.
PURPOSE
To report the levels of the novel total and H-specific growth differentiation factor-15 (GDF-15) and other established hormonal systems and to describe hormonal patterns in controls and patients with MASLD and its stages.
METHODS
This is a multicenter study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven MASLD (n = 374) and Controls (n = 81) were recruited.
RESULTS
We report for the first time that total and H-specific GDF-15 levels are higher in MASLD, at-risk metabolic dysfunction associated steatohepatitis (MASH), and severe fibrosis than in Controls. In addition, follistatin-like-3 (FSTL-3), free insulin-like growth factor-1 (IGF-1), leptin, and insulin levels were higher in MASLD patients than in Controls, while adiponectin levels were lower in MASLD subjects than in Controls. Activin-A, follistatin (FST), FSTL-3, and insulin levels significantly increased in severe fibrosis compared to no/mild fibrosis, while free IGF-1 decreased. In addition, adiponectin levels were lower in subjects without fibrosis vs. any fibrosis. Moreover, GDF-15 presented a strong positive association for the likelihood of having MASLD and at-risk MASH, while in adjusted analyses, FST and adiponectin showed inverse associations. Two different patterns of at-risk MASH were revealed through unsupervised analysis (total variation explained=54%). The most frequent pattern met in our sample (34.3%) was characterized by higher levels of total and H-specific GDF-15, follistatins, and activins, as well as low adiponectin levels. The second pattern revealed was characterized by high levels of free IGF-1, insulin, and leptin, with low levels of activin-A and adiponectin. Similar patterns were also generated in the case of overall MASLD.
CONCLUSIONS
Total and H-specific GDF-15 levels increase as MASLD severity progresses. FSTL-3, free IGF-1, leptin, and insulin are also higher, whereas adiponectin and activin-A levels are lower in the MASLD group than in Controls. Hormonal systems, including GDF-15, may not only be involved in the pathophysiology but could also prove useful for the diagnostic workup of MASLD and its stages and may potentially be of therapeutic value.
Topics: Humans; Leptin; Insulin-Like Growth Factor I; Non-alcoholic Fatty Liver Disease; Follistatin; Growth Differentiation Factor 15; Adiponectin; Insulin; Activins; Fibrosis; Biopsy
PubMed: 37757973
DOI: 10.1016/j.metabol.2023.155694 -
Biomolecules Nov 2023Adipokines are essential mediators produced by adipose tissue and exert multiple biological functions. In particular, adiponectin, leptin, resistin, IL-6, MCP-1 and... (Review)
Review
Adipokines are essential mediators produced by adipose tissue and exert multiple biological functions. In particular, adiponectin, leptin, resistin, IL-6, MCP-1 and PAI-1 play specific roles in the crosstalk between adipose tissue and other organs involved in metabolic, immune and vascular health. During obesity, adipokine imbalance occurs and leads to a low-grade pro-inflammatory status, promoting insulin resistance-related diabetes and its vascular complications. A causal link between obesity and gut microbiota dysbiosis has been demonstrated. The deregulation of gut bacteria communities characterizing this dysbiosis influences the synthesis of bacterial substances including lipopolysaccharides and specific metabolites, generated via the degradation of dietary components, such as short-chain fatty acids, trimethylamine metabolized into trimethylamine-oxide in the liver and indole derivatives. Emerging evidence suggests that these bacterial metabolites modulate signaling pathways involved in adipokine production and action. This review summarizes the current knowledge about the molecular links between gut bacteria-derived metabolites and adipokine imbalance in obesity, and emphasizes their roles in key pathological mechanisms related to oxidative stress, inflammation, insulin resistance and vascular disorder. Given this interaction between adipokines and bacterial metabolites, the review highlights their relevance (i) as complementary clinical biomarkers to better explore the metabolic, inflammatory and vascular complications during obesity and gut microbiota dysbiosis, and (ii) as targets for new antioxidant, anti-inflammatory and prebiotic triple action strategies.
Topics: Humans; Adipokines; Gastrointestinal Microbiome; Insulin Resistance; Dysbiosis; Obesity; Bacteria
PubMed: 38136564
DOI: 10.3390/biom13121692 -
Pathology Oncology Research : POR 2023Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are... (Review)
Review
Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are contributed to the etiology of MM. Notably, studies have shown that obesity increases the risk of MM and worsens outcomes for MM patients. Adipokines play an important role in mediating the close association between MM and metabolic derangements. In this review, we summarize the epidemiologic studies to show that the risk of MM is increased in obese. Accumulating clinical evidence suggests that adipokines could display a correlation with MM. and studies have shown that adipokines are linked to MM, including roles in the biological behavior of MM cells, cancer-associated bone loss, the progression of MM, and drug resistance. Current and potential therapeutic strategies targeted to adipokines are discussed, proposing that adipokines can guide early patient diagnosis and treatment.
Topics: Humans; Multiple Myeloma; Adipokines; Risk Factors; Obesity
PubMed: 37637774
DOI: 10.3389/pore.2023.1611338