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( −)-Epicatechin and cardiometabolic risk factors: a focus on potential mechanisms of action

  • Invited Review
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Abstract

This review summarizes experimental evidence on the beneficial effects of ( −)-epicatechin (EC) attenuating major cardiometabolic risk factors, i.e., dyslipidemias, obesity (adipose tissue dysfunction), hyperglycemia (insulin resistance), and hypertension (endothelial dysfunction). Studies in humans are revised and complemented with experiments in animal models, and cultured cells, aiming to understand the molecular mechanisms involved in EC-mediated effects. Firstly, an assessment of EC metabolism gives relevance to both conjugated-EC metabolites product of host metabolism and microbiota-derived species. Integration and analysis of results stress the maintenance of redox homeostasis and mitigation of inflammation as relevant processes associated with cardiometabolic diseases. In these processes, EC appears having significant effects regulating NADPH oxidase (NOX)–dependent oxidant production, nitric oxide (NO) production, and energy homeostasis (mitochondrial biogenesis and function). The potential participation of cell membranes and membrane-bound receptors is also discussed in terms of direct molecular action of EC and EC metabolites reaching cells and tissues.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

ADME:

Absorption digestion metabolism and excretion

AKT:

Protein kinase B

AMP:

Adenosine monophosphate

AMPK:

5′-AMP-activated protein kinase

Apo:

Apolipoprotein

BCAEC:

Bovine coronary artery endothelial cells

BP:

Blood pressure

CaM:

Calmodulin

CaMKII:

CaM-dependent protein kinase II

C/EBPα:

CCAAT/enhancer-binding protein alpha

CCL:

Chemokine (C–C motif) ligand

CRP:

C-reactive protein

DOCA:

Deoxycorticosterone acetate

EC:

( −)-Epicatechin

eNOS:

Endothelial NOS

ERK:

Extracellular signal–regulated protein kinase

ET1:

Endothelin 1

FAS:

Fatty acid synthase

FMD:

Flow-mediated dilation

GLP1:

Glucagon-like peptide 1

GLUT2:

Glucose transporter 2

gp91 phox:

Glycoprotein 91 phagocytic oxidase (NOX2 catalytic subunit)

GPER:

G protein–coupled estrogen receptor

GSH:

Glutathione

HCAEC:

Human coronary artery endothelial cells

HDL:

High-density lipoprotein

HF:

High-fat

HFD:

HF diet

HOMA:

Homeostatic model assessment

HUVEC:

Human umbilical vein endothelial cells

ICAM:

Intercellular adhesion molecule

IKK:

IκB kinase

IL:

Interleukin

iNOS:

Inducible NOS

IR:

Insulin resistance

IRS1:

Insulin receptor substrate 1

IκBα:

NFκB inhibitor alpha

JNK:

C-Jun N-terminal kinases

LDL:

Low-density lipoprotein

L-NAME:

L-nitro-arginine methyl ester

MCP1:

Monocyte chemoattractant protein 1

NFκB:

Nuclear factor of kappa light polypeptide gene enhancer in B cells

nNOS:

Neuronal NOS

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX:

NADPH-oxidase

Nrf:

Nuclear factor erythroid related factor

p22phox:

Protein 22 phagocytic oxidase

p47phox:

Protein 47 phagocytic oxidase

PDK1:

Protein 3-phosphoinositide-dependent protein kinase 1

PGC1α:

Peroxisome proliferator-activated receptor γ coactivator 1 alpha

PI3K:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PPAR:

Peroxisome proliferator-activated receptor

PTP1B:

Protein-tyrosine phosphatase 1B

RFM:

Ring fission metabolite

SGLT:

Sodium-glucose co-transporter

SREBP:

Sterol regulatory element binding proteins

SREM:

Structurally related EC metabolite

Tfam:

Mitochondrial transcription factor A

TG:

Triglycerides

TNFα:

Tumor necrosis factor alpha

TRPV3:

Transient receptor potential vanilloid channel 3

UCP:

Uncoupling protein

VCAM:

Vascular cell adhesion molecule

WAT:

White adipose tissue

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Funding

This work was supported by grants from University of Buenos Aires, Argentina, 20020170100586BA (MG) and 20020190100157BA (CGF), National Scientific and Technical Research Council-Argentina PIP11220170100585CO (MG), and National Agency for Scientific and Technological Promotion, Argentina PICT2018-03052 (MG).

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  1. Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Universidad de Buenos Aires, Junín 956, 1113, Buenos Aires, Argentina

    Ezequiel J. Hid, Juana I. Mosele, Paula D. Prince, Cesar G. Fraga & Monica Galleano

  2. Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina

    Ezequiel J. Hid, Juana I. Mosele, Paula D. Prince, Cesar G. Fraga & Monica Galleano

  3. Department of Nutrition, University of California, Davis, CA, 95616, USA

    Cesar G. Fraga

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Hid, E.J., Mosele, J.I., Prince, P.D. et al. ( −)-Epicatechin and cardiometabolic risk factors: a focus on potential mechanisms of action. Pflugers Arch - Eur J Physiol 474, 99–115 (2022). https://doi.org/10.1007/s00424-021-02640-0

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