Variable Changes of Circulating ANGPTL3 and ANGPTL4 in Different Obese Phenotypes: Relationship with Vasodilator Dysfunction

Obesity associates with premature atherosclerosis and an increased burden of cardiovascular disease, especially when accompanied by abnormalities of lipid and glucose metabolism. Angiopoietin-like (ANGPTL)3 and ANGPTL4 are metabolic regulators, whose upregulation is associated with dyslipidemia, insulin resistance and atherosclerosis. We analyzed, therefore, changes in circulating ANGPTL3 and ANGPTL4 in obese patients with different metabolic phenotypes and their relation with impaired vasodilator reactivity, an early abnormality in atherosclerosis. Compared to the lean subjects (n = 42), circulating ANGPTL3 was elevated (both p > 0.001) in the patients with metabolically unhealthy obesity (MUO; n = 87) and type 2 diabetes (T2D; n = 31), but not in those with metabolically healthy obesity (MHO; n = 48, p > 0.05). Circulating ANGPTL4, by contrast, was increased in all obese subgroups (all p < 0.001 vs. lean subjects). Vasodilator responses to both acetylcholine and sodium nitroprusside were reduced in the three obese subgroups vs. lean subjects (all p < 0.001), with greater impairment in the patients with T2D than in those with MHO and MUO (all p < 0.05). In the whole population, an inverse relationship (r = 0.27; p = 0.003) was observed between circulating ANGPTL4 and endothelium-dependent vasorelaxation. Circulating ANGPTL3 and ANGPTL4 undergo variable changes in obese patients with different metabolic phenotypes; changes in ANGPTL4 relate to endothelial dysfunction, making this protein a possible target for vascular prevention in these patients.

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Association of Metabolically Healthy and Unhealthy Obesity Phenotype with Markers Related to Obesity, Diabetes among Young, Healthy Adult Men. Analysis of MAGNETIC Study

Life ◽

10.3390/life11121350 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1350

Author(s):

Mateusz Lejawa ◽

Kamila Osadnik ◽

Zenon Czuba ◽

Tadeusz Osadnik ◽

Natalia Pawlas

Keyword(s):

Plasminogen Activator Inhibitor ◽

Normal Weight ◽

Obese Patients ◽

Metabolically Healthy Obesity ◽

Plasminogen Activator Inhibitor 1 ◽

Metabolic Markers ◽

Adult Men ◽

Metabolically Healthy Obese ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity

Adipose tissue secretes many regulatory factors called adipokines. Adipokines affect the metabolism of lipids and carbohydrates. They also influence the regulation of the immune system and inflammation. The current study aimed to evaluate the association between markers related to obesity, diabesity and adipokines and metabolically healthy and unhealthy obesity in young men. The study included 98 healthy participants. We divided participants into three subgroups based on body mass index and metabolic health definition: 49 metabolically healthy normal-weight patients, 27 metabolically healthy obese patients and 22 metabolically unhealthy obese patients. The 14 metabolic markers selected were measured in serum or plasma. The analysis showed associations between markers related to obesity, diabesity and adipokines in metabolically healthy and unhealthy obese participants. The decreased level of adipsin (p < 0.05) was only associated with metabolically healthy obesity, not with metabolically unhealthy obesity. The decreased level of ghrelin (p < 0.001) and increased level of plasminogen activator inhibitor-1 (p < 0.01) were only associated with metabolically unhealthy obesity, not with metabolically healthy obesity. The decreased level of adiponectin and increased levels of leptin, c-peptide, insulin and angiopoietin-like 3 protein were associated with metabolically healthy and unhealthy obesity. In conclusion, our data show that metabolically healthy obesity was more similar to metabolically unhealthy obesity in terms of the analyzed markers related to obesity and diabesity.

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Heterogeneity of obesity phenotypes in relation to cardiovascular risk

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2019-1-161-167 ◽

2019 ◽

Vol 18 (1) ◽

pp. 161-167

Author(s):

М. A. Druzhilov ◽

Т. Yu. Kuznetsova

Keyword(s):

Cardiovascular Risk ◽

Cardiovascular Diseases ◽

Metabolic Disorders ◽

Metabolically Healthy Obesity ◽

Wide Range ◽

Obesity Phenotype ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity ◽

Complications And Mortality

Obesity is associated with numerous metabolic disorders, the development and progression of a wide range of conditions and diseases, primarily cardiovascular disease and type 2 diabetes. One of the widely discussed phenomena of the association of obesity with cardiovascular diseases, their complications and mortality is the phenomenon of “heterogeneity of obesity phenotypes in relation to cardiovascular risk”. Currently, two main phenotypes have been identified — metabolically healthy and metabolically unhealthy obesity. At the same time, not only the expediency of separation, but also the existence of this phenotype is widely discussed today. The article provides an overview of existing approaches to the verification of metabolic phenotypes of obesity and data relating to the epidemiology and the association of metabolically healthy obesity with the risk of cardiovascular diseases and death, and also discusses the factors that determine the features of the obesity phenotype.

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Heterogeneity of obesity phenotypes in relation to cardiovascular risk

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2019-1-162-168 ◽

2019 ◽

Vol 18 (1) ◽

pp. 161-167 ◽

Cited By ~ 1

Author(s):

М. A. Druzhilov ◽

Т. Yu. Kuznetsova

Keyword(s):

Cardiovascular Risk ◽

Cardiovascular Diseases ◽

Metabolic Disorders ◽

Metabolically Healthy Obesity ◽

Wide Range ◽

Obesity Phenotype ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity ◽

Complications And Mortality

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FAT-FREE MASS, METABOLICALLY HEALTHY OBESITY, AND TYPE 2 DIABETES IN SEVERELY OBESE ASIAN ADULTS

Endocrine Practice ◽

10.4158/ep171792.or ◽

2017 ◽

Vol 23 (8) ◽

pp. 915-922 ◽

Cited By ~ 1

Author(s):

Pornpoj Pramyothin ◽

Vichol Limpattanachart ◽

Suwitcha Dawilai ◽

Rungnapha Sarasak ◽

Chariya Sukaruttanawong ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fat Free Mass ◽

Metabolically Healthy Obesity ◽

Severely Obese ◽

Metabolically Healthy

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Comparison between metabolically healthy obesity and metabolically unhealthy obesity by different definitions among Mexican children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0077 ◽

2020 ◽

Vol 33 (2) ◽

pp. 215-222 ◽

Cited By ~ 2

Author(s):

María Lola Evia-Viscarra ◽

Rodolfo Guardado-Mendoza

Keyword(s):

Blood Pressure ◽

Family Background ◽

Density Lipoprotein ◽

Model Assessment ◽

Metabolically Healthy Obesity ◽

Cvd Risk ◽

Cross Sectional ◽

Mexican Children ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity

AbstractBackgroundThere is no consensus on the definition of metabolically healthy obesity (MHO) and the diagnostic criteria in children.ObjectivesTo estimate the prevalence of MHO and compare clinical and biochemical characteristics between MHO and metabolically unhealthy obesity (MUO), and to evaluate the association between MUO and cardiovascular disease (CVD) risk, anthropometrics and family background using different definitions in children.MethodsThis was a cross-sectional study. Participants included 224 obese children between the years 2007 and 2017. MHO was defined by three different criteria: (i) absence of metabolic syndrome (MHO-MS), (ii) no insulin resistance (IR) by homeostatic model assessment (HOMA) <3.16 cut-off (MHO-IR3.16) and (iii) absence of IR at <95th percentile for Mexican children (MHO-95th).ResultsThe prevalence of MHO-MS, MHO-IR3.16 and MHO-IR95th was 12.9%, 56.3% and 41.5%, respectively. The prevalence of simultaneous MHO-MS plus MHO-IR95th was 5.36%. Children with MHO-MS vs. MUO-MS showed lower height, weight and body mass index (BMI) percentiles; MHO-IR3.16 vs. MUO-IR3.16 showed lower age, acanthosis, Tanner, waist circumference (WC), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and glucose; and MHO-IR95th vs. MUO-IR95th showed lower acanthosis, WC, DBP, glucose and high high-density lipoprotein cholesterol (HDL-C). MUO-MS was associated with WC > 90th, type 2 diabetes mellitus (T2DM) in first-degree relatives and obesity in siblings. MUO-IR3.16 was associated with pubertal stages, WC > 90th, WHtR > 0.55 and fasting hyperglycemia. MUO-IR95th was associated with WHtR > 0.55 and HDL < 10th. MHO-MS and MHO-IR3.16 or MHO-IR95th did not have agreement.ConclusionsThe prevalence of MHO varied depending on the definition, although the real MHO with no MS or IR is very low. Low DBP and high HDL-C in MHO were present in any definition. Association of MUO with anthropometric, biochemical and family background differs across definitions.

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Metabolically Healthy Obesity

Endocrine Reviews ◽

10.1210/endrev/bnaa004 ◽

2020 ◽

Vol 41 (3) ◽

pp. 405-420 ◽

Cited By ~ 28

Author(s):

Matthias Blüher

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Diseases ◽

Cell Function ◽

Obesity Treatment ◽

Individual Risk ◽

Metabolically Healthy Obesity ◽

Glucose And Lipid Metabolism ◽

Metabolically Healthy ◽

Safe Condition

Abstract Obesity contributes to reduced life expectancy, impaired quality of life, and disabilities, mainly in those individuals who develop cardiovascular diseases, type 2 diabetes, osteoarthritis, and cancer. However, there is a large variation in the individual risk to developing obesity-associated comorbid diseases that cannot simply be explained by the extent of adiposity. Observations that a proportion of individuals with obesity have a significantly lower risk for cardiometabolic abnormalities led to the concept of metabolically healthy obesity (MHO). Although there is no clear definition, normal glucose and lipid metabolism parameters—in addition to the absence of hypertension—usually serve as criteria to diagnose MHO. Biological mechanisms underlying MHO lower amounts of ectopic fat (visceral and liver), and higher leg fat deposition, expandability of subcutaneous adipose tissue, preserved insulin sensitivity, and beta-cell function as well as better cardiorespiratory fitness compared to unhealthy obesity. Whereas the absence of metabolic abnormalities may reduce the risk of type 2 diabetes and cardiovascular diseases in metabolically healthy individuals compared to unhealthy individuals with obesity, it is still higher in comparison with healthy lean individuals. In addition, MHO seems to be a transient phenotype further justifying therapeutic weight loss attempts—even in this subgroup—which might not benefit from reducing body weight to the same extent as patients with unhealthy obesity. Metabolically healthy obesity represents a model to study mechanisms linking obesity to cardiometabolic complications. Metabolically healthy obesity should not be considered a safe condition, which does not require obesity treatment, but may guide decision-making for a personalized and risk-stratified obesity treatment.

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Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice

Journal of Diabetes Research ◽

10.1155/2017/4108768 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Britta Noebauer ◽

Alexander Jais ◽

Jelena Todoric ◽

Klaus Gossens ◽

Hedwig Sutterlüty-Fall ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Obese Patients ◽

Metabolically Healthy Obesity ◽

Naturally Occurring ◽

Obesity And Diabetes ◽

Inflammatory Processes ◽

Experimental Approaches ◽

Metabolically Healthy

Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes. 25-Hydroxycholesterol (25-OHC) is produced in cells from cholesterol by the enzyme cholesterol 25-hydroxylase (Ch25h) and is involved in lipid metabolism, inflammatory processes, and cell proliferation. Here, we investigated the role of hepatic Ch25h in the transition from metabolically healthy obesity to insulin resistance and diabetes. Using several different experimental approaches, we demonstrated the significance of Ch25h on the border of “healthy” and “diseased” states of obesity. Adenovirus-mediated Ch25h overexpression in mice improved glucose tolerance and insulin sensitivity and lowered HOMA-IR. Our data suggest that low hepatic Ch25h levels could be considered a risk marker for unhealthy obesity.

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