EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice

Bessi, Valérie L.; Labbé, Sébastien M.; Huynh, David; Ménard, Liliane; Jossart, Christian; Febbraio, Maria; Guérin, Brigitte; Bentourkia, M’hamed; Lecomte, Roger; Carpentier, André C.; Ong, Huy; Marleau, Sylvie

doi:10.1093/cvr/cvs225

Cited by 49 publications

(65 citation statements)

References 41 publications

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“…Our results confirm the ability to iWAT to undergo browning after chronic CL and cold and to exhibit increased mtDNA content. However, our results do not demonstrate that the browning of iWAT was paralleled by a major increase in its metabolic activity as assessed with a triad of PET tracers that have been proven to readily detect any metabolic changes in BAT (3,4,19,33) as well as in other metabolically active tissues such as heart or liver (2,8,21,29,46). The oxidative activity ([ 11 C]acetate) of iWAT following chronic CL and cold was not only trivial compared with that of iBAT, but it was also not higher than that of eWAT, which resisted browning.…”

Section: Discussioncontrasting

confidence: 84%

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Labbé

Caron

Chechi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal role in energy metabolism. Brown adipocytes can also be found in white adipose tissue (WAT) depots [e.g., inguinal WAT (iWAT)] following adrenergic stimulation, and they have been referred to as “beige” adipocytes. Whether the presence of these adipocytes, which gives iWAT a beige appearance, can confer a white depot with some thermogenic activity remains to be seen. In consequence, we designed the present study to investigate the metabolic activity of iBAT, iWAT, and epididymal white depots in mice. Mice were either 1) kept at thermoneutrality (30°C), 2) kept at 30°C and treated daily for 14 days with an adrenergic agonist [CL-316,243 (CL)], or 3) housed at 10°C for 14 days. Metabolic activity was assessed using positron emission tomography imaging with fluoro-[18F]deoxyglucose (glucose uptake), fluoro-[18F]thiaheptadecanoic acid (fatty acid uptake), and [11C]acetate (oxidative activity). In each group, substrate uptakes and oxidative activity were measured in anesthetized mice in response to acute CL. Our results revealed iBAT as a major site of metabolic activity, which exhibited enhanced glucose and nonesterified fatty acid uptakes and oxidative activity in response to chronic cold and CL. On the other hand, beige adipose tissue failed to exhibit appreciable increase in oxidative activity in response to chronic cold and CL. Altogether, our results suggest that the contribution of beige fat to acute-CL-induced metabolic activity is low compared with that of iBAT, even after sustained adrenergic stimulation.

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Section: Discussioncontrasting

confidence: 84%

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Labbé

Caron

Chechi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…The same model of HF could also be rescued by lipoprotein lipase deficiency, further substantiating the importance of excess lipid delivery to this cardiomyopathy phenotype (29). Similar results have also been obtained in other models of diabetic CM using pharmacologic approaches to inhibit CD36 (6,12). Thus, preventing excess lipid delivery as a means to reduce mitochondrial stress may be a viable approach to reverse or prevent early stages of diabetic CM.…”

Section: Metabolic Modulationsupporting

confidence: 67%

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Schilling

2015

Antioxidants & Redox Signaling

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Significance: Diabetes is an important risk factor for the development of heart failure (HF). Given the increasing prevalence of diabetes in the population, strategies are needed to reduce the burden of HF in these patients. Recent Advances: Diabetes is associated with several pathologic findings in the heart including dysregulated metabolism, lipid accumulation, oxidative stress, and inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a central mediator of these pathologic responses. The development of therapeutic approaches targeting mitochondrial biology holds promise for the management of HF in diabetic patients. Critical Issues: Despite significant data implicating mitochondrial pathology in diabetic cardiomyopathy, the optimal pharmacologic approach to improve mitochondrial function remains undefined. Future Directions: Detailed mechanistic studies coupled with more robust clinical phenotyping will be necessary to develop novel approaches to improve cardiac function in diabetes. Moreover, understanding the interplay between diabetes and other cardiac stressors (hypertension, ischemia, and valvular disease) will be of the utmost importance for clinical translation of scientific discoveries made in this field. Antioxid. Redox Signal. 22, 1515Signal. 22, -1526

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“…Using short-term inducible cardiomyocytespecific CD36 ablation we tested the hypotheses that: 1) icCD36KO mouse hearts have reduced FA uptake, utilization and storage and 2) this alteration in cardiac substrate utilization leads to improved post-ischemic functional recovery. These studies will allow us to determine if the concept of a combined strategy of limiting FA uptake and partially inhibiting FAO is a beneficial therapeutic approach to reducing ischemic injury [24,25].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery

Nagendran

Pulinilkunnil

Kienesberger

et al. 2013

Journal of Molecular and Cellular Cardiology

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EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice

Abstract: Our results show that pretreatment with EP 80317 protected the heart against damage and dysfunction elicited by MI/R, along with a transient reduction in peripheral lipolysis. Our findings support CD36 as a novel target for the treatment of ischaemic cardiopathy.

Cited by 49 publications

References 41 publications

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery

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