DNAJB3

Mechanisms that drive addiction to sugar rich foods are a major driving factor in the pathogenesis of obesity, which has become one of the most significant health care burdens. The molecular underpinnings of these hedonic mechanisms that drive addiction to sugar are poorly understood. The investigators demonstrated that methylglyoxal (MGO) derived Advanced Glycation Endproducts (AGEs) enhance food intake especially under a high sugar diet. The investigators identified a methylglyoxal (MGO) lowering cocktail, Gly-low, a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine that demonstrates a multimodal effect influencing many pathways related to aging including calorie restriction. Glycation lowering (Gly-low) treatment significantly reduces food intake and weight gain in the db/db mice that lack the leptin receptor. The investigators also extended the lifespan of C57BL/6 mice fed with these compounds starting when they were 24 months old. Based on these results, the investigators hypothesized that methylglyoxal (MGO) lowering cocktail of compounds can be given to adults with obesity, specified as body mass index (BMI) >27, to lower serum and urinary markers of insulin resistance, lower boy mass index (BMI), and lower food intake.

Background:
Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron [MG]) combined with a supplement (alpha-lipoic acid [ALA]) may help.
Objective:
To learn how MG and ALA can help the body process food.
Eligibility:
People aged 18 to 65 years with a body mass index between 30 and 40 kg/m2.
Design:
Participants will be screened. They will have a physical exam. They will have blood and urine tests and a test of their heart function. They will speak with a dietician.
The study has two phases. Each phase begins with a 2-day stay in the clinic; then the participant will take the study drugs at home for about 4 weeks, followed by another 2-day stay in the clinic. They will also have outpatient visits about 2 weeks after each clinic stay.
During the clinic stays, participants will undergo many tests:
They will have a plastic tube (catheter) inserted into a vein in each arm. These will be used to draw blood and to infuse glucose (sugar) and insulin.
They will have imaging scans.
They will have a clear hard plastic shield placed over their head to measure oxygen and carbon dioxide as they breathe.
Participants will take the study drugs at home. Both MG and ALA are taken by mouth with water. During one phase, participants will take MG plus a placebo. A placebo looks like the study drug but doesn t contain medicine.
They will log their diet, exercise, and sleep....

The goal of this clinical trial is to test alpha lipoic acid in children undergoing hemodialysis. The main questions it aims to answer are:
* Will the use of alpha lipoic acid lower cardiovascular events in that population?
* Is the incidence of those cardiovascular events linked to the oxidative stress and endothelial dysfunction in that population?
* Will the drug cause side effects?
Participants will:
* take either one dose daily of 600mg tablet Alpha lipoic acid orally or a look-alike tablet containing no drug.
* be monitored for the occurrence of cardiovascular events (stroke, angina, etc.)
* be monitored for the occurrence of side effects
* give blood samples for testing serum levels of E-selectin biomarker and superoxide dismutase enzyme
* undergo clinical examinations (Echocardiogram, Duplex ultrasonography, Intima-Media-Thickness) Researchers will compare between the group taking alpha lipoic acid and the group taking the look-alike tablet.