In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments. Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver. Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1β, IL-6, IFNγ) and anti-inflammatory TNFα were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome. In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFNγ) was observed. This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities.Molecules 2020, 25, 23 2 of 15 the development of new, safer and more effective pharmaceutical approaches for obesity treatment is essential.Natural water is a mixture of molecules containing stable isotopes 16 O, 17 O, 18 O, 1 H, and 2 H. The ratio of deuterium atoms to protium (D/H) in fresh and marine water is 132-156 µg/g (ppm) [7,8].Since the mass of protium H is half of the mass of deuterium D, effects arising from the replacement of isotopes influence biological systems; for example, the rates of chemical reactions between substances containing these isotopes may differ by a factor of 5-10 [9-11].Numerous publications over the last 20 years have been devoted to the study of the role of deuterium in natural (150 ppm) or reduced content in the human body [12]. It has been shown that deuterium-depleted water (DDW) exhibits antidotal properties with individual and combined effects on the dosage of pharmaceutical substances and auxiliary substances [13][14][15][16]. The mechanisms of such influence are due to the structure, physicochemical properties of DDW [17] and changes in ligand-receptor interactions in biological objects of different hierarchical levels [18]. DDW increases the rate of photosynthesis and promotes the growth of plants and aquatic animals [19,20]. In Europe, the USA, Japan, China and Russia, DDW is used for prophylactic and therapeutic purposes [21,22]. Currently, DDW is using as an adjuvant in cancer treatment ...
