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Metabolically Healthy Obesity is not a Myth: A Case Report

ABSTRACT: People with obesity who do not have the metabolic syndrome or components of the metabolic syndrome have been characterized as having metabolically healthy obesity (MHO). However, the existence of MHO has been questioned because people with MHO are at greater risk of developing diabetes and fatal cardiovascular disease than people who are lean and healthy. A 25 year-old woman with rigorously defined MHO (based on normal oral glucose tolerance, insulin sensitivity (assessed by using the hyperinsulinemic-euglycemic clamp procedure), plasma triglyceride and HDL-cholesterol, intrahepatic triglyceride content and carotid intima-media thickness [CIMT]) was evaluated at baseline (BMI=37.7 kg/m2) and 5 years later, after gaining 30.8 kg (32%) in weight (BMI=49.6 kg/m2). The increase in weight was comprised of an 8.8 kg (20%) increase in FFM, 22.0 kg (42%) increase in total body fat, 8.1 kg (37%) increase in leg fat mass, 57% increase in subcutaneous abdominal fat and a 78% in intra-abdominal fat. Weight gain did not have adverse effects on fasting plasma glucose, oral glucose tolerance, beta-cell function, insulin sensitivity, plasma triglyceride, intrahepatic triglyceride content and CIMT. Adipose tissue expression of genes involved in extracellular matrix formation did not change. Adipose tissue expression of several inflammation-related genes increased by more than 30%, but was not associated with a corresponding increase in plasma cytokine concentrations, with the exception of an increase in plasma IL-6. The present case study demonstrates that some people with obesity are resistant to the adverse cardiometabolic effects of excess adiposity and marked weight gain.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217154 | GEO | 2023/11/01

REPOSITORIES: GEO

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Project description:Background & Aims: Non-alcoholic fatty liver disease accompanies obesity and is independently associated with cardiovascular disease. Omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid, reduce the risk of cardiovascular disease due to their anti-inflammatory and hypolipidemic effects. Recent data suggested that metabolic effects of EPA/DHA as marine phospholipids could be stronger than triglycerides (fish oil). We characterised the mechanisms underlying beneficial effects of EPA/DHA phospholipids alone or in combination with antidiabetic drugs on hepatosteatosis in dietary obese mice. Methods: Male C57BL/6N mice were fed for 7 weeks a corn oil-based high-fat diet (cHF) or subjected to cHF-based interventions: (i) cHF with DHA/EPA as phosphatidylcholine-rich concentrate replacing ~10 % of dietary lipids (PC); ii) cHF with a low-dose of thiazolidinedione rosiglitazone (10 mg/kg diet), which retains some of the beneficial effects but also potentiates hepatic lipid accumulation (R); and iii) PC+R. Metabolic profiling together with hepatic gene expression and lipidomic analyses were performed. Results: PC and PC+R prevented weight gain and glucose intolerance induced by cHF, while all interventions reduced abdominal fat and plasma triglycerides. In contrast to R, PC and PC+R lowered hepatic and plasma cholesterol and eliminated hepatosteatosis. Hepatic microarray analysis primarily revealed a complex downregulation of lipogenic and cholesterol biosynthesis pathways by PC. Lipidomic analysis identified arachidonic acid, DHA and EPA in hepatic phosphatidylcholine and phosphatidylethanolamine fractions as the most important variables. Importantly, down-regulation of genes within these pathways was enlarged by phospholipid versus triglyceride forms of EPA/DHA in an independent experiment. Conclusions: Obesity-associated hepatosteatosis and hypercholesterolemia were ameliorated by marine phospholipids in association with a complex inhibition of biosynthetic pathways in liver. Stronger effects of phospholipids versus triglyceride form of EPA/DHA suggest their preferential use in the prevention and possible treatment of obesity-associated metabolic hepatic dysfunctions.

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Metabolically Healthy Obesity is not a Myth: A Case Report

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