Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors

Abstract

Background: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.Methods: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.Results: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.Conclusion: The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

A new use for old drugs: identifying compounds with an anti-obesity effect using a high through-put semi-automated Caenorhabditis elegans screening platform

“…Strikingly, Lamivudine was able to significantly reduce fat in an nhr-49 /PPAR mutant background, suggesting the effects of this drug will be applicable as an anti-obesity intervention in people with Metabolic Syndrome. Similarly, when Midodrine is administered to rats, the expression of PPAR was upregulated or activated resulting in a lowering of fat and body weight [ 50 , 51 ]. We also found that worms exposed to Midodrine displayed a reduction in fat content, and in a PPAR mutant background the fat reduction was even more striking.…”

α1-Adrenergic Receptors: Insights into Potential Therapeutic Opportunities for COVID-19, Heart Failure, and Alzheimer’s Disease

“…The current hypothesis is that selective α 1A -AR agonists may be a potential treatment in heart failure [ 54 , 55 ], since chronic α 1B -AR stimulation, as evidenced through transgenic mouse models, appears to be maladaptive by inducing dilated cardiomyopathy [ 29 ] or heart failure [ 37 ]. While α-AR blockers are a current treatment option for heart failure, using α 1A -AR selective agonists may provide potentially greater benefits such as preventing dementia [ 56 ], improving metabolic function and glucose tolerance [ 56 , 57 , 58 ], increasing lifespan with reduce cancer risk [ 59 , 60 ] and reducing inflammation and cataracts [ 58 , 61 ].…”