Pathology of metabolically-related dyslipidemia

doi:10.1016/j.cca.2021.06.029

Clinica Chimica Acta

Volume 521, October 2021, Pages 107-115

https://doi.org/10.1016/j.cca.2021.06.029 Get rights and content

Highlights

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Metabolic related dyslipidemia is characterized by increased LDL-C, TG, and accompanied by lower HDL-C.
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Metabolic related dyslipidemia is mainly driven by insulin resistance and pro-inflammatory cytokines.
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Metabolic related dyslipidemia induces alterations in microenvironment of adipocytes and hepatocytes.
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Immune cells present infiltration and functional alteration under the status of dyslipidemia.
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Further data focusing on the novel bio-markers in dyslipidemia might upgrade therapeutic approaches.

Abstract

It is well established that overweight/obesity is closely associated with multiple health problems. Among these, dyslipidemia is the most important and main driving force behind pathologic development of cardio-metabolic disorders such as diabetes mellitus, atherosclerotic-related cardiovascular disease and hypertension. Notably, a subtype of dyslipidemia, metabolic related dyslipidemia, is now recognized as a vital link between obesity and multiple different cardiovascular diseases. This condition is characterized by increased low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) and very low density lipoprotein cholesterol (VLDL-C) as well as decreased high density lipoprotein cholesterol (HDL-C) in serum. In this review, we summarize the current understanding of metabolic related dyslipidemia and the potential mechanisms which lead to the pathogenesis of obesity/overweight. We focus on several novel lipid biomarkers such as pro-protein convertase subtilisin/kexin type 9 (PCSK9) and sphingosine-1-phosphate (S1P) and their potential use as biomarkers of metabolic related dyslipidemia.

Introduction

It is well established that overweight/obesity, characterized by body mass index (BMI) greater than 30 kg/m², is closely associated with several health problems such as insulin resistance, hypertension and atherosclerotic-related cardiovascular disease [1]. Among these, dyslipidemia has been identified as most important and the main driving force behind the pathological development of cardio-metabolic disorders. According to the latest published findings, the subtype of dyslipidemia, arising from concerted action of insulin resistance and obesity, has recently been renamed as “metabolic related dyslipidemia”, which is defined as increased serum low density lipoprotein cholesterol (LDL-C), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-C), accompanied by relatively decreased serum high density lipoprotein cholesterol (HDL-C) [2]. However, the underlying mechanisms are still not clearly elucidated. Herein, in the present review, we summarized the current understanding of metabolic related dyslipidemia and the potential mechanisms by which metabolic related dyslipidemia facilitates the pathological development of obesity and the related cardiovascular diseases. Furthermore, we also summarized the novel published results which focused on several novel lipid biomarkers in the pathogenesis of metabolic related dyslipidemia, such as pro-protein convertase subtilisin/kexin type 9 (PCSK9), microRNAs, and sphingosine-1-phosphate (S1P), and their potential use as novel biomarkers of metabolic related dyslipidemia.

Section snippets

Role of insulin resistance in modulating the process of metabolic related dyslipidemia

The important function of insulin and insulin resistance on modulating the serum lipid catabolism under the condition of metabolic related dyslipidemia are being well elucidated according to the emerging results. As is reported previously, insulin could significantly inhibit the process of lipolysis within adipose tissue through suppressing the activity of hormone-sensitive lipase (HSL), which is the key enzyme in affecting the intracellular lipid metabolism. As a result, insulin controls the

Traditional bio-markers in metabolic related dyslipidemia

Indeed, different traditional bio-markers have various metabolic effects in modulating the pathophysiological conditions under the condition of metabolic related dyslipidemia. Interestingly, the relationship between diverse traditional bio-markers with dyslipidemia has been considered as the most important topic of current investigations during the past several decades. Special interest has been concerned on their inflammatory modulation aspects.

Novel bio-markers in metabolic related dyslipidemia

Currently, the knowledge of the complex link between metabolic related dyslipidemia and cardio-metabolic disorder risk is being expanded with the exploration of potential mechanisms. In this paragraph, the dyslipidemia-related alterations of several novel discovered modulators of metabolism of lipid profiles, including secreted frizzled-related protein (SFRP) 5, C1q/TNF-related proteins (CTRPs), and PCSK9, will be deeply discussed.

Conclusions and future perspectives

Up to date, the pathological progression of metabolic related dyslipidemia has been considered to be closely correlated with multiple cardio-metabolic disturbances and inflammatory response. Under the condition of dyslipidemia, several metabolic related cell types, including hepatocytes, macrophages, and adipocytes, are dysfunctional with aberrant intracellular lipid metabolism; furthermore, the microenvironment of diverse tissues, such as the liver and the adipose tissue, are also changed with

Author contributions

Xin Su, Xiang Chen, and Bin Wang contributed to the study design; Xin Su wrote the manuscript. All authors reviewed drafts and approved the final version of the manuscript.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Funding

Not received.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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ReviewPathology of metabolically-related dyslipidemia

Highlights

Abstract

Introduction

Section snippets

Role of insulin resistance in modulating the process of metabolic related dyslipidemia

Traditional bio-markers in metabolic related dyslipidemia

Novel bio-markers in metabolic related dyslipidemia

Conclusions and future perspectives

Author contributions

Ethical approval

Funding

Declaration of Competing Interest

Metabolism

Diabetes Res Clin Pract

J Am Coll Cardiol

Biochim Biophys Acta Mol Cell Biol Lipids

Nat Prod Res

Trends Cell Biol

Clin Genitourin Cancer

Toxicol Lett

Biomed Pharmacother

Prog Cardiovasc Dis

Metabolism

Nutrition

Atherosclerosis

Int J Cardiol

Exp Cell Res

Atherosclerosis

Metabolism

Arch Biochem Biophys

Mol Cell Proteomics

Int J Biochem Cell Biol

Biomed Pharmacother

J Reprod Immunol

Diabetes Res Clin Pract

Fish Shellfish Immunol

Mol Cell Endocrinol

Atherosclerosis

Gene

J Thromb Haemost

Cytotherapy

Am J Pathol

J Biol Chem

Heart Lung Circ

Diabetes Metab Syndr

Dyslipidemia in obesity: mechanisms and potential targets

Nutrients

Metabolic signals and innate immune activation in obesity and exercise

Exerc Immunol Rev

The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation

Adv Exp Med Biol

The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux

J Clin Invest

Obesity-driven disruption of haematopoiesis and the bone marrow niche

Nat Rev Endocrinol

IL-32alpha-induced inflammation constitutes a link between obesity and colon cancer

Oncoimmunology

Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients

PLoS ONE

Invariant natural killer T cells in adipose tissue: novel regulators of immune-mediated metabolic disease

Cell Mol Life Sci

Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1

J Mol Cell Biol

Subcutaneous Fat Fibrosis Links Obesity to Insulin Resistance in Chinese Americans

J Clin Endocrinol Metab

Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance

Endocrinology

Role of Perivascular Adipose Tissue in Health and Disease

Compr Physiol

Epicardial fat: more than just an “epi” phenomenon?

Horm Metab Res

Comparative assessments of crucial factors for a functional ligand-targeted nanocarrier

J Drug Target

Metabolic and hormonal disturbances in women with epilepsy on antiepileptic drug monotherapy

Epilepsia

Stress and obesity as risk factors in cardiovascular diseases: a neuroimmune perspective

J Neuroimmune Pharmacol

Leptin and Inflammation

Curr Immunol Rev

Review
Pathology of metabolically-related dyslipidemia