Adiponectin, driver or passenger on the road to insulin sensitivity?

Ye, Risheng; Scherer, Philipp E.

doi:10.1016/j.molmet.2013.04.001

Cited by 223 publications

(223 citation statements)

References 107 publications

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“…However, during instances of increased metabolic demand (such as fasting or b3-adrenergic stimulation), Cidea does not inhibit mobilization of the fatty acids from triglyceride stores and therefore allows the important metabolic switch from carbohydrates to fatty acids. The increased circulating levels of adiponectin also contribute to the preferential storage of triglycerides in adipose tissue 41 and improve metabolic flexibility and insulin sensitivity 40,45 .…”

Section: Discussionmentioning

confidence: 99%

Cidea improves the metabolic profile through expansion of adipose tissue

Abreu-Vieira

Fischer²,

Mattsson

et al. 2015

Nat Commun

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In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

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Section: Discussionmentioning

confidence: 99%

Cidea improves the metabolic profile through expansion of adipose tissue

Abreu-Vieira

Fischer²,

Mattsson

et al. 2015

Nat Commun

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“…Fasting glucose levels are mainly determined by hepatic glucose production, whereas increased 2-h glucose mainly reflects peripheral glucose uptake (22). Adiponectin receptors (ADIPOR)-1 and 2 are expressed on both hepatocytes and skeletal muscle cells with ADIPOR2 being the predominant receptor in the liver and ADIPOR1 being the predominant receptor in skeletal muscle (23). Therefore, it can be speculated that ADIPOR2-mediated signalling and downstream effects on peroxisome proliferatoractivated receptor-α and regulation of glucose uptake, fatty acid oxidation, oxidative stress and inflammation may mediate the observed association between adiponectin and deterioration of fasting glycaemia in our study.…”

Section: Subclinical Inflammation and Glycaemiamentioning

confidence: 99%

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

Herder

Færch

Carstensen‐Kirberg

et al. 2016

European Journal of Endocrinology

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Objective: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and methods: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. Results: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammationrelated processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function. European Journal of Endocrinology175:5 368 Clinical Study C Herder and others Inflammation and glucose metabolism

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“…Much of the evidence that adiponectin is an insulin sensitiser come from murine studies. Genetic ablation of the adiponectin-encoding gene in mice produced IR in some, though not all reports, while administration of various different oligomeric adiponectin preparations has been shown in mice to improve insulin sensitivity (64,65). The metabolic role of adiponectin in humans is less clear.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

Semple¹

2016

European Journal of Endocrinology

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Insulin orchestrates physiological responses to ingested nutrients; however, although it elicits widely ramifying metabolic and trophic responses from diverse tissues, 'insulin resistance (IR)', a pandemic metabolic derangement commonly associated with obesity, is usually defined solely by blunting of insulin's hypoglycaemic effect. Recent study of monogenic forms of IR has established that biochemical subphenotypes of IR exist, clustering into those caused by primary disorders of adipose tissue and those caused by primary defects in proximal insulin signalling. IR is often first recognised by virtue of its associated disorders including type 2 diabetes, dyslipidaemia (DL), fatty liver and polycystic ovary syndrome (PCOS). Although these clinically observed associations are confirmed by cross-sectional and longitudinal population-based studies, causal relationships among these phenomena have been more difficult to establish. Single gene IR is important to recognise in order to optimise clinical management and also permits testing of causal relationships among components of the IR syndrome using the principle of Mendelian randomisation. Thus, where a precisely defined genetic defect is identified that directly produces one component of the syndrome, then phenomena that are causally linked to that component should be seen. Where this is not the case, then a simple causal link is refuted. This article summarises known forms of monogenic severe IR and considers the lessons to be learned about the pathogenic mechanisms both upstream from common IR and those downstream linking it to disorders such as DL, fatty liver, PCOS and cancer.

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Adiponectin, driver or passenger on the road to insulin sensitivity?

Cited by 223 publications

References 107 publications

Cidea improves the metabolic profile through expansion of adipose tissue

Cidea improves the metabolic profile through expansion of adipose tissue

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

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