The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic β-Cell Survival and Insulin Secretion

Natalicchio, Annalisa; Marrano, Nicola; Biondi, Giuseppina; Spagnuolo, Rosaria; Labarbuta, Rossella; Porreca, Immacolata; Cignarelli, Angelo; Bugliani, Marco; Marchetti, Piero; Perrini, Sebastio; Laviola, Luigi

doi:10.2337/db17-0002

Cited by 102 publications

(100 citation statements)

References 26 publications

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“…Irisin is a PPARγ-coactivator-1α (PGCα)-dependent myokine that stimulates browning in subcutaneous adipose tissues and induces increased energy expenditure, which improves obesity and IR through the MAPK and ERK pathways [92,93]. Irisin also stimulates beta-cell survival and glucose-stimulated insulin secretion through the PGA pathway, and inhibits saturated fatty acid-induced apoptosis in pancreatic beta-cells [94]. A low level of irisin in mice with muscle-specific constitutive ROCK1 activation suppresses irisin production in muscles, decreasing browning in adipocytes and leading to impaired insulin sensitivity [95].…”

Section: Irisinmentioning

confidence: 99%

Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences

Hong

Choi

2020

IJMS

195

151

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The prevalence of sarcopenic obesity is increasing worldwide, particularly amongst aging populations. Insulin resistance is the core mechanism of sarcopenic obesity and is also associated with variable cardiometabolic diseases such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Fat accumulation in muscle tissue promotes a proinflammatory cascade and oxidative stress, leading to mitochondrial dysfunction, impaired insulin signaling, and muscle atrophy. To compound the problem, decreased muscle mass aggravates insulin resistance. In addition, the crosstalk between myokines and adipokines leads to negative feedback, which in turn aggravates sarcopenic obesity and insulin resistance. In this review, we focus on the molecular mechanisms linking sarcopenic obesity and insulin resistance with various biological pathways. We also discuss the impact and mechanism of sarcopenic obesity and insulin resistance on cardiometabolic disease.

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Section: Irisinmentioning

confidence: 99%

Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences

Hong

Choi

2020

IJMS

195

151

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“…Indeed, diabetic mice injected with irisin show better glycemic and lipid profiles . We have recently demonstrated that, following 2‐week daily administration of irisin intraperitoneally, mice display an improved glucose tolerance, as a result of enhanced glucose‐stimulated insulin secretion, and this is associated with increased insulin content, as well as larger pancreatic beta‐cell area and cell proliferation …”

Section: Introductionmentioning

confidence: 99%

“…8 We have recently demonstrated that, following 2-week daily administration of irisin intraperitoneally, mice display an improved glucose tolerance, as a result of enhanced glucosestimulated insulin secretion, and this is associated with increased insulin content, as well as larger pancreatic beta-cell area and cell proliferation. 10 In addition to the pancreas, the biological functions of irisin include metabolic effects on multiple other tissues, such as bone, 11,12 skeletal muscle, liver, and fat. 8 Furthermore, numerous studies reported that circulating irisin levels are reduced in patients with type 2 diabetes, while increased serum or plasma irisin levels correlate with pathological conditions of energy surfeit, such as overweight/obesity, polycystic ovary syndrome (PCOS), and metabolic syndrome, probably in response to deterioration of insulin sensitivity or to compensate an underlying irisin resistance.…”

mentioning

confidence: 99%

Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

Natalicchio

Marrano

Biondi

et al. 2019

Diabetes Metabolism Res

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Background Irisin, a newly discovered muscle‐derived hormone, acts in different organs and tissues, improving energy homeostasis. In this study, we assessed, for the first time, the effects of intraperitoneal irisin injections on circulating levels of leptin and ghrelin, mRNA expression of the major hypothalamic appetite regulators and brain neurotrophic factors, as well as feeding behaviour in healthy mice. Methods Twelve male 6‐week‐old C57BL/6 mice were randomized into two groups and intraperitoneally injected daily with irisin (0.5 μg/g body weight) or vehicle (phosphate‐buffered saline [PBS]) for 14 days. On the last day of observation, leptin and ghrelin levels were measured with an enzyme‐linked immunosorbent assay (ELISA). mRNA levels of genes of interest were analysed by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in brain extracts. Results Irisin administration did not change leptin or ghrelin serum concentrations. However, irisin injection increased CART, POMC, NPY, and BDNF mRNA levels, without affecting the mRNA expression of AgRP, orexin, PMCH, and UCP2. Finally, over the time frame of irisin treatment, body weight and feeding behaviour were unaltered. Conclusions These results suggest that intraperitoneal injection of irisin, although without effects on feeding behaviour and body weight, can increase the expression of anorexigenic and neurotrophic genes in mouse brain.

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“…In addition, a recent study has shown that irisin suppresses apoptosis in β cells and islets under lipotoxic condition via modulation of protein kinase B/B-cell lymphoma 2 (BCL2) signaling pathway [23]. However, it has yet to be determined whether irisin can alleviate lipid metabolic disorder and pro-inflammatory actions in β cells under T2DM-like conditions.…”

Section: Introductionmentioning

confidence: 99%

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

Zhang¹,

Xie²,

Leung³

2018

Cell Physiol Biochem

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Background/Aims: Islet metabolic disorder and inflammation contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Irisin is a recently identified adipomyokine with protective effects on metabolic homeostasis and inflammation-suppressing effects in hepatic and vascular cells. The present study examined the effects of irisin on lipid metabolism and inflammation in β cells under glucolipotoxic conditions. Methods: Rat INS-1E β cells and islets isolated from C57BL/6 mice were incubated in glucolipotoxic conditions with or without irisin. Intracellular lipid contents and lipogenic gene expression were determined by enzymatic colorimetric assays and real-time PCR, respectively. Inflammatory status was evidenced by Western blot analysis for the phosphorylation of nuclear factor-κB (NF-κB) p65 and real-time PCR analysis for the expression of pro-inflammatory genes. Results: Irisin reversed glucolipotoxicity-induced intracellular non-esterified fatty acid (NEFA) and triglyceride accumulation, suppressed associated elevations in lipogenic gene expression, and phosphorylated acetyl-CoA-carboxylase (ACC) in INS-1E cells. These demonstrated effects were dependent on irisin-activated adenosine monophosphate-activated protein kinase (AMPK). Meanwhile, AMPK signaling mediated the protective effects of irisin on INS-1E cell insulin secretory ability and survival as well. Additionally, irisin inhibited phosphorylation of NF-κB p65 while decreasing the expression of pro-inflammatory genes in INS-1E cells under glucolipotoxic conditions. Moreover, irisin also improved insulin secretion, inhibited apoptosis, and restored β-cell function-related gene expression in isolated mouse islets under glucolipotoxic conditions. Conclusion: Irisin attenuated excessive lipogenesis in INS-1E cells under glucolipotoxic state through activation of AMPK. Irisin also suppressed overnutrition-induced inflammation in INS-1E cells. Our findings implicate irisin as a promising therapeutic target for the treatment of islet lipid metabolic disorder and islet inflammation in T2DM.

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The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic β-Cell Survival and Insulin Secretion

Cited by 102 publications

References 26 publications

Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences

Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences

Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions

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