Insulin resistance persists despite a metabolically healthy obesity phenotype

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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Rey-López et al. Respond to “The Metabolically Healthy Obesity Phenotype”

American Journal of Epidemiology ◽

10.1093/aje/kwv179 ◽

2015 ◽

Vol 182 (9) ◽

pp. 745-746 ◽

Cited By ~ 1

Author(s):

Juan Pablo Rey-López ◽

Leandro Fornias de Rezende ◽

Thiago Hérick de Sá ◽

Emmanuel Stamatakis

Keyword(s):

Metabolically Healthy Obesity ◽

Obesity Phenotype ◽

Metabolically Healthy

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THE CHARACTERISTICS OF SECRETION OF ADIPONECTIN AND ITS RELATIONSHIP WITH PARTICULAR INDICESOF METABOLISM IN MALES OF ABLE-BODIED AGE IN CASE OF OBESITY

Medical Journal of the Russian Federation ◽

10.18821/0869-2106-2017-23-6-312-315 ◽

2017 ◽

Vol 23 (6) ◽

pp. 312-315

Author(s):

Olga V. Karataeva

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Low Density Lipoproteins ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Metabolically Healthy Obesity ◽

Significant Difference ◽

Fasting Glycaemia ◽

Metabolically Healthy ◽

Degree Of Severity

The sampling consisted of 79 examined males of able-bodied age. The arterial hypertension stage I and II was established in 58% of them; obesity of various degree of severity was diagnosed in 63% of them; metabolic syndrome according criteria ATP-III was noted in 46.8% of examined patients. The general clinical and anthropometric examination was carried out. The laboratory analyses included estimation of lipidogram, fasting glycaemia and also hormones adiponectin and insulin with following calculation of index of insulin resistance HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). The study was organized to investigate effecting of obesity on secretion of adiponectin and its relationship with indices of lipidogram and level of insulin resistance. The comparative analysis of groups with and absence of obesity established no significant difference in level of adiponectin and indices of lipidogram. the significant differences were established in the levels of basal insulin hence in value of index NOMA-IR that points to hyperinsulinemia and expressed insulin resistance in patients with obesity. The patients were separated in two groups depending on presence of manifestations of metabolic syndrome: with metabolically healthy obesity and metabolically complicated obesity. The analysis established a significant decreasing of level of adiponectin in the group of metabolically complicated obesity accompanied by insulin resistance, dyslipidemia and increased level of glycaemia. The study established no effect of degree of obesity on decreasing of level of adiponectin. The significant differences between levels of adiponectin in comparison between group without obesity and group of metabolically healthy obesity. The correlation analysis in group with obesity demonstrated back-coupling between level of adiponectin and content of total cholesterol, low density lipoproteins and coefficient of atherogenicity. The comparison of groups according median of adiponectin established significant differences in rate of development of metabolic syndrome and value of coefficient of atherogenicity.

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Metabolically healthy obesity: predictors of transformation to unhealthy phenotype in St Petersburg population (according to the ESSE-RF study)

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2021-27-3-279-290 ◽

2021 ◽

Vol 27 (3) ◽

pp. 279-290

Author(s):

M. A. Boyarinova ◽

O. P. Rotar ◽

A. M. Erina ◽

N. A. Paskar ◽

A. S. Alieva ◽

...

Keyword(s):

Insulin Resistance ◽

Uric Acid ◽

Waist Circumference ◽

Low Density Lipoprotein ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Metabolically Healthy Obesity ◽

Metabolically Healthy ◽

Over Time

Objective. The purpose of the study was to determine the dynamics of the metabolically healthy obesity (MHO) status according to the Meigs criteria, and to establish the predictors of the transformation of healthy obesity phenotype into an unhealthy (MUHO) one in the population of residents of St Petersburg (Russia) at 6,5-year follow-up. Design and methods. Within the epidemiology study ESSE-RF a random sample of 1600 St Petersburg inhabitants stratiﬁed according to gender and age was formed. Examination of participants included anthropometry with measurement of waist circumference and calculation of body mass index (BMI), measurement of blood pressure (BP), fasting blood glucose, insulin (index of insulin resistance was calculated), creatinine, cortisol, lipid spectrum, C-reactive protein, adiponectin, leptin, and uric acid. Meigs MHO criteria (2006) were used in obese subjects (BMI > 30 kg/m²). Obese patients, who were identiﬁed as metabolically healthy in 2012–2013, were invited for follow-up in 2018–2019. Results. At the ﬁrst stage obesity was diagnosed in 430 (26,9 %) participants, according to the BMI, 116 (27,0 %) of them were metabolically healthy according to the Meigs criteria. At follow-up, 44,4% individuals with the MHO phenotype transformed to the MUHO category on average after 6,5 years. Individuals who retained the MHO phenotype over time had signiﬁcantly lower baseline systolic BP and diastolic BP levels, more favorable lipid levels and lower levels of uric acid, insulin, and index of insulin resistance. Glucose increase by every 0,5 mmol/l and higher was associated with elevated probability of transformation MHO to MUHO phenotype by 10,9 times (adjusted for sex and age). Conclusions. Signiﬁcantly higher levels of BP, insulin resistance, low density lipoprotein and uric acid at baseline, as well as an increase in glucose levels over time, were associated with the transformation of the metabolically healthy to the unhealthy phenotype in obese individuals at 6,5-year follow-up. In all individuals with the MHO phenotype, there was a signiﬁcant increase in waist circumference over time, accompanied by an increase in BMI only in those who transformed into the MUHO status.

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