Elsevier

Metabolism

Volume 92, March 2019, Pages 71-81
Metabolism

Obesity and dyslipidemia

https://doi.org/10.1016/j.metabol.2018.11.005Get rights and content

Highlights

  • Obesity is mainly driven by insulin resistance and pro-inflammatory adipokines.

  • Vitamin D deficiency affects adipose tissue function and lipid status in obesity.

  • Metabolically healthy obesity is characterised by a favorable lipid profile.

  • Further data on PCSK9 and S1P in obesity might upgrade therapeutic approaches.

Abstract

Obesity, a pandemic of the modern world, is intimately associated with dyslipidemia, which is mainly driven by the effects of insulin resistance and pro-inflammatory adipokines. However, recent evidence suggests that obesity-induced dyslipidemia is not a unique pathophysiological entity, but rather has distinct characteristics depending on many individual factors. In line with that, in a subgroup of metabolically healthy obese (MHO) individuals, dyslipidemia is less prominent or even absent. In this review, we will address the main characteristics of dyslipidemia and mechanisms that induce its development in obesity. The fields, which should be further investigated to expand our knowledge on obesity-related dyslipidemia and potentially yield new strategies for prevention and management of cardiometabolic risk, will be highlighted. Also, we will discuss recent findings on novel lipid biomarkers in obesity, in particular proprotein convertase subtilisin/kexin type 9 (PCSK9), as the key molecule that regulates metabolism of low-density lipoproteins (LDL), and sphingosine-1-phosphate (S1P), as one of the most important mediators of high-density lipoprotein (HDL) particles function. Special attention will be given to microRNAs and their potential use as biomarkers of obesity-associated dyslipidemia.

Introduction

Weight gain, as a response to overnutrition and reduced energy expenditure, leads to overweight and obesity, conditions associated with intensive processes of hyperplasia and hypertrophy of adipocytes [1]. Also, obesity is accompanied by macrophages infiltration into the adipose tissue, followed by a switch of their phenotype from anti-inflammatory M2 to pro-inflammatory M1 [2]. All these changes in adipose tissue composition are associated with altered adipokines secretion and development of adipose tissue dysfunction (adiposopathy) which is responsible for obesity-related metabolic diseases [3].

Insulin resistance/hyperinsulinemia is the most common metabolic disorder in obesity and it is the main driving force behind the development of dyslipidemia. In recent years, the form of dyslipidemia arising from concerted action of insulin resistance and obesity is recognized as "metabolic dyslipidemia" [4]. High concentrations of triglycerides (TG) accompanied by decreased high-density lipoprotein cholesterol (HDL-C) concentrations are its main characteristics. Low-density lipoprotein cholesterol (LDL-C) concentrations could be optimal or mildly increased, although the number of LDL particles (LDL-P) can be increased [5]. Dyslipidemia is an important link between obesity and the development of type 2 diabetes mellitus, cardiovascular disease (CVD) and certain types of cancer [6].

Section snippets

Pathways of metabolic dyslipidemia development

Accumulating evidence suggests that insulin resistance is the most probable link between obesity and obesity-associated metabolic dyslipidemia [4]. According to Magkos et al. [7] insulin resistance and metabolic dyslipidemia are associated with adiposopathy. As previously demonstrated, adiposopathy is characterised by several structural and functional changes in adipose tissue [2,3]. These abnormalities also have detrimental effects on adipocyte intracellular structure, leading to endoplasmic

Metabolically healthy and metabolically unhealthy obesity — the role of dyslipidemia

Metabolically healthy obesity (MHO) is the term used to designate a subgroup of obese subjects without obvious detrimental consequences of increased weight [69]. In addition, a subset of lean subjects with metabolic disturbances has also been recognized and categorized as metabolically unhealthy normal weight subjects (MUNW) [70]. To date, numerous authors proposed various definitions of MHO, which could be summarised as the absence of the following metabolic disturbances: abdominal obesity,

Novel biomarkers of dyslipidemia in obesity

Over the last decade, the knowledge of the complex link between dyslipidemia and cardiovascular risk has been further expanded with the introduction of novel mechanisms and molecules, constituting potential biomarkers or therapeutic targets. Here, we will discuss obesity-related changes of two recently discovered biomarkers and modulators of LDL metabolism and HDL functionality, i.e. PCSK9 and sphingosine-1-phosphate (S1P), respectively. In addition, functional role of microRNAs and potential

Implications for cardiovascular disease prevention

Despite significant preventive and therapeutic efforts, development of CVD remains the principal unfavourable outcome of obesity. With an aim to reduce the overall risk for cardiovascular and other chronic complications, clinical practice guidelines for management of obesity acknowledge that the treatment of co-morbidities should be integral part of the obese patients' care [170]. Specific guidelines for the treatment of dyslipidemia in obesity are recently released by the European Society of

Conclusion

Impaired production of adipokines and chronic low-grade inflammation in adipose tissue form the base for insulin resistance, which is the main driving force in the development of metabolic dyslipidemia in obesity. In addition, numerous epidemiological data linked vitamin D deficiency and metabolic dyslipidemia, although a clear demonstration of causal relationship is still lacking. The concept of MHO has been recently recognised, indicating a transitional state of relative protection against

Acknowledgment

This work was granted by the Ministry of Education, Science and Technological Development, Republic of Serbia [Project No. 175035] and supported by the COST Action CA16113.

Author contribution

All authors equally contributed to the present work.

Declarations of interest

None.

References (175)

  • Z. Hu et al.

    Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance

    Diabetes Res Clin Pract

    (2013)
  • M.A. Abbas

    Physiological functions of vitamin D in adipose tissue

    J Steroid Biochem Mol Biol

    (2017)
  • I.N. Sergeev

    1,25-Dihydroxyvitamin D3 induces Ca2+-mediated apoptosis in adipocytes via activation of calpain and caspase-12

    Biochem Biophys Res Commun

    (2009)
  • J.R. Lupton et al.

    Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study

    J Clin Lipidol

    (2016)
  • A. Vitezova et al.

    Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study

    Maturitas

    (2015)
  • R. Jorde et al.

    Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids

    Prog Lipid Res

    (2011)
  • J.L. Pérez-Castrillón et al.

    Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease

    Am J Cardiol

    (2007)
  • K. Liang et al.

    Role of secondary hyperparathyroidism in the genesis of hypertriglyceridemia and VLDL receptor deficiency in chronic renal failure

    Kidney Int

    (1998)
  • H. Mathew et al.

    Metabolic health and weight: understanding metabolically unhealthy normal weight or metabolically healthy obese patients

    Metabolism

    (2016)
  • N. Stefan et al.

    Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans

    Cell Metab

    (2017)
  • Y. Song et al.

    Comparison of usefulness of body mass index versus metabolic risk factors in predicting 10-year risk of cardiovascular events in women

    Am J Cardiol

    (2007)
  • C.M. Phillips et al.

    Lipoprotein particle subclass profiles among metabolically healthy and unhealthy obese and non-obese adults: does size matter?

    Atherosclerosis

    (2015)
  • G. Iacobellis et al.

    Small, dense low-density lipoprotein and C-reactive protein in obese subjects with and without other criteria for the metabolic syndrome

    J Clin Lipidol

    (2007)
  • S. Kim et al.

    Predominance of small dense LDL differentiates metabolically unhealthy from metabolically healthy overweight adults in Korea

    Metabolism

    (2014)
  • K.C. Sung et al.

    Obesity and incidence of diabetes: effect of absence of metabolic syndrome, insulin resistance, inflammation and fatty liver

    Atherosclerosis

    (2018)
  • M. Janghorbani et al.

    Risk of diabetes according to the metabolic health status and degree of obesity

    Diabetes Metab Syndr

    (2017)
  • C.G. Gonçalves et al.

    Metabolically healthy obese individuals: key protective factors

    Nutrition

    (2016)
  • C.S. Chang et al.

    Role of adiponectin gene variants, adipokines and hydrometry-based percent body fat in metabolically healthy and abnormal obesity

    Obes Res Clin Pract

    (2018)
  • J.A. Morrison et al.

    Paradoxically high adiponectin and the healthy obese phenotype in obese black and white 16 year old girls

    Transl Res

    (2010)
  • J.N. Jones Buie et al.

    The role of miRNAs in cardiovascular disease risk factors

    Atherosclerosis

    (2016)
  • E.J. Abente et al.

    MicroRNAs in obesity-associated disorders

    Arch Biochem Biophys

    (2016)
  • H. Yaribeygi et al.

    MicroRNAs and type 2 diabetes mellitus: molecular mechanisms and the effect of antidiabetic drug treatment

    Metabolism

    (2018)
  • X. Cui et al.

    Change in circulating microRNA profile of obese children indicates future risk of adult diabetes

    Metabolism

    (2018)
  • J.D. Horton et al.

    Molecular biology of PCSK9: its role in LDL metabolism

    Trends Biochem Sci

    (2007)
  • L.A. Muir et al.

    Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity

    Obesity (Silver Spring)

    (2016)
  • A. Castoldi et al.

    The macrophage switch in obesity development

    Front Immunol

    (2016)
  • B. Klop et al.

    Dyslipidemia in obesity: mechanisms and potential targets

    Nutrients

    (2013)
  • R.J. Koene et al.

    Shared risk factors in cardiovascular disease and cancer

    Circulation

    (2016)
  • F. Magkos et al.

    Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augment metabolic dysfunction

    Obesity (Silver Spring)

    (2010)
  • O.T. Hardy et al.

    What causes the insulin resistance underlying obesity?

    Curr Opin Endocrinol Diabetes Obes

    (2012)
  • G. Boden et al.

    Free fatty acids in obesity and type 2 diabetes: defining their role in development of insulin resistance and β-cell dysfunction

    Eur J Clin Investig

    (2002)
  • M.E. Hass et al.

    The regulation of ApoB metabolism by insulin

    Trends Endocrinol Metab

    (2013)
  • B. Draznin

    Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin

    Diabetes

    (2006)
  • R. Ringseis et al.

    Metabolic signals and innate immune activation in obesity and exercise

    Exerc Immunol Rev

    (2015)
  • A. Engin

    The pathogenesis of obesity-associated adipose tissue inflammation

    Adv Exp Med Biol

    (2017)
  • V.T. Samuel et al.

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

    J Clin Invest

    (2016)
  • M.C. Petersen et al.

    Mechanisms of insulin action and resistance

    Physiol Rev

    (2018)
  • A.J. Knights et al.

    Adipokines and insulin action

    Adipocyte

    (2014)
  • J.E. Pessin et al.

    Adipokines mediate inflammation and insulin resistance

    Front Endocrinol (Lausanne)

    (2013)
  • F. Lönnqvist

    The obese (ob) gene and its product leptin—a new route toward obesity treatment in man?

    Q J Med

    (1996)
  • Cited by (344)

    • Protein kinase D (PKD) on the crossroad of lipid absorption, synthesis and utilization

      2024, Biochimica et Biophysica Acta - Molecular Cell Research
    View all citing articles on Scopus
    View full text