Cyclodextrin counteracts obesity associated with various diseases including susceptibility for Covid-19

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Obesity has become a worldwide health crisis and is associated with a plethora of comorbidities. Cardiovascular disease (CVD) and type 2 diabetes are well known consequences , but also psychosocial, neurological, pulmonary, gastrointestinal, renal, musculoskeletal and (other) endocrine disorders can be linked to obesity. The question on the blog of Science was “Why COVID-19 is more deadly in people with obesity—even if they’re young?” Most recently the largest descriptive study yet of hospitalized U.S. COVID-19 patients, posted as a preprint last month by Genentech researchers, found that 77% of nearly 17,000 patients hospitalized with COVID-19 were overweight (29%) or obese (48%). (The Centers for Disease Control and Prevention defines overweight as having a BMI of 25 to 29.9 kilograms per square meter, and obesity as a BMI of 30 or greater.)

Another study captured the rate of COVID-19 hospitalizations among more than 334,000 people in England. Published last month in the Proceedings of the National Academy of Sciences, it found that although the rate peaked in people with a BMI of 35 or greater, it began to rise as soon as someone tipped into the overweight category.

The physical pathologies that render people with obesity vulnerable to severe COVID-19 begin with mechanics: Fat in the abdomen pushes up on the diaphragm, causing that large muscle, which lies below the chest cavity, to impinge on the lungs and restrict airflow. This reduced lung volume leads to collapse of airways in the lower lobes of the lungs, where more blood arrives for oxygenation than in the upper lobes. In addition to this mechanical barrier also enhanced clotting in the lung blood vessels and impaired immune system increase the risk of intensive care need in Covid-19.

Scantlebery et al. (2018) published a study on feeding obese mice on Western diet (19% protein, 11% fat and 70% carbohydrate) with 20% (w/v) HPBCD (4000 mg/kg body weight). In this murine model of Western diet-induced obesity (DIO model), it was shown that the liver and kidney respond differently to lipid overload. This is most likely linked to their natural roles in lipid metabolism. The western diet resulted in the accumulation of lipid droplets in both the liver and kidney, but phospholipidosis (intralysosomal accumulation of phospholipids) was observed exclusively in the kidneys. It was shown that 2-HP-CD is effective in preventing weight gain, lowering plasma cholesterol levels and reducing the accumulation of both polar (phospholipids) and nonpolar (TG/cholesterol) lipids. In addition, HPBCD led to extensive tubular vacuolation and damage, but did not result in renal dysfunction. 

Angelique M. L. Scantlebery, Peter Ochodnicky, Lotte Kors, Elena Rampanelli, Loes M. Butter, Chaima El Boumashouli, Nike Claessen, Gwen J. Teske, Marius A. van den Bergh Weerman, Jaklien C. Leemans, Joris J. T. H. Roelofs, and Sandrine Florquin (2019) β-Cyclodextrin counteracts obesity in Western diet-fed mice but elicits a nephrotoxic effect. Sci Rep. 9: 17633. doi: 10.1038/s41598-019-53890-z

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