Obesity and 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)
Adipose tissue dysfunction contributes to obesity related metabolic diseases
Best Pract Res Clin Endocrinol Metab
(2013)- et al.
Clinical implications of discordance between low-density lipoprotein cholesterol and particle number
J Clin Lipidol
(2011) - et al.
Endoplasmic reticulum stress in obesity and obesity-related disorders: an expanded view
Metabolism
(2016) - et al.
Insulin effects in muscle and adipose tissue
Diabetes Res Clin Pract
(2011) - et al.
High-density lipoprotein and coronary heart disease: current and future therapies
J Am Coll Cardiol
(2010) - et al.
From excess adiposity to insulin resistance: the role of free fatty acids
Vasc Pharmacol
(2012) - et al.
From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation
Nutr Metab Cardiovasc Dis
(2009) - et al.
NF-Kb, inflammation and metabolic disease
Cell Metab
(2011) - et al.
Interleukin-10 facilitates both cholesterol uptake and efflux in macrophages
J Biol Chem
(2009) - et al.
Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype
J Biol Chem
(2010)
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
Physiological functions of vitamin D in adipose tissue
J Steroid Biochem Mol Biol
1,25-Dihydroxyvitamin D3 induces Ca2+-mediated apoptosis in adipocytes via activation of calpain and caspase-12
Biochem Biophys Res Commun
Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study
J Clin Lipidol
Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study
Maturitas
Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids
Prog Lipid Res
Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease
Am J Cardiol
Role of secondary hyperparathyroidism in the genesis of hypertriglyceridemia and VLDL receptor deficiency in chronic renal failure
Kidney Int
Metabolic health and weight: understanding metabolically unhealthy normal weight or metabolically healthy obese patients
Metabolism
Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans
Cell Metab
Comparison of usefulness of body mass index versus metabolic risk factors in predicting 10-year risk of cardiovascular events in women
Am J Cardiol
Lipoprotein particle subclass profiles among metabolically healthy and unhealthy obese and non-obese adults: does size matter?
Atherosclerosis
Small, dense low-density lipoprotein and C-reactive protein in obese subjects with and without other criteria for the metabolic syndrome
J Clin Lipidol
Predominance of small dense LDL differentiates metabolically unhealthy from metabolically healthy overweight adults in Korea
Metabolism
Obesity and incidence of diabetes: effect of absence of metabolic syndrome, insulin resistance, inflammation and fatty liver
Atherosclerosis
Risk of diabetes according to the metabolic health status and degree of obesity
Diabetes Metab Syndr
Metabolically healthy obese individuals: key protective factors
Nutrition
Role of adiponectin gene variants, adipokines and hydrometry-based percent body fat in metabolically healthy and abnormal obesity
Obes Res Clin Pract
Paradoxically high adiponectin and the healthy obese phenotype in obese black and white 16 year old girls
Transl Res
The role of miRNAs in cardiovascular disease risk factors
Atherosclerosis
MicroRNAs in obesity-associated disorders
Arch Biochem Biophys
MicroRNAs and type 2 diabetes mellitus: molecular mechanisms and the effect of antidiabetic drug treatment
Metabolism
Change in circulating microRNA profile of obese children indicates future risk of adult diabetes
Metabolism
Molecular biology of PCSK9: its role in LDL metabolism
Trends Biochem Sci
Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity
Obesity (Silver Spring)
The macrophage switch in obesity development
Front Immunol
Dyslipidemia in obesity: mechanisms and potential targets
Nutrients
Shared risk factors in cardiovascular disease and cancer
Circulation
Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augment metabolic dysfunction
Obesity (Silver Spring)
What causes the insulin resistance underlying obesity?
Curr Opin Endocrinol Diabetes Obes
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
The regulation of ApoB metabolism by insulin
Trends Endocrinol Metab
Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin
Diabetes
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: intergrating signaling pathways and substrate flux
J Clin Invest
Mechanisms of insulin action and resistance
Physiol Rev
Adipokines and insulin action
Adipocyte
Adipokines mediate inflammation and insulin resistance
Front Endocrinol (Lausanne)
The obese (ob) gene and its product leptin—a new route toward obesity treatment in man?
Q J Med
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