Background The aim of this study was to investigate the anti-obesity effects of DWP16001, a sodium-glucose cotransporter-2 (SGLT2 inhibitor), in naturally obese dogs. A total of 20 dogs were divided into four equal groups: one obese control (OC group), and three treated groups; DWP0.2 group, DWP0.5 group, and DWP1 group. OC group fed with food for maintenance and treated groups were fed with food for maintenance with 0.2 mg/kg DWP16001, 0.5 mg/kg DWP16001 and 1 mg/kg DWP16001, respectively. The food for maintenance was provided to dogs as 2 RER (Resting energy requirement) in kcal and DWP16001-supplemented food was administered once a day for 8 weeks. Results Body condition score, body weight, and fat thickness were significantly reduced (P < 0.05) in the DWP0.2 group compared with the OC group, respectively without affecting the food consumption. At the 10th week the food consumption rate was 101.35 ± 2.56, 166.59 ± 4.72, 98.47 ± 1.44 and 123.15 ± 2.45% compared with initial food consumption rate. Body fat percentage, chest and waist circumference, blood glucose, and insulin were reduced compared to OC group but not significantly different from those of the OC group during experimental period. Serum alanine aminotransferase, alkaline phosphatase, creatine phosphokinase, and creatinine were significantly reduced in DWP0.2 group on 8 weeks. Serum cholesterol and triglycerides were reduced but not significantly. No specific adverse effects were observed throughout the experiment, and hematological parameters were unchanged. The results indicate that DWP16001 was not harmful to the dogs in our study and might have anti-obesity effects in naturally obese dogs. Conclusions The above results and discussion suggest that DWP16001 is safe and might have anti-obesity effects in naturally obese dogs.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with systemic inflammation and immune modulation. Previously, we have shown that extracellular vesicles resulting from human adipose-tissue-derived mesenchymal stem cells (ASC-EVs) attenuated AD-like symptoms by reducing the levels of multiple inflammatory cytokines. Here, we aimed to investigate the improvement of canine AD upon using canine ASC-exosomes in a Biostir-induced AD mouse model. Additionally, we conducted in vivo toxicity studies to determine whether they targeted organs and their potential toxicity. Firstly, we isolated canine ASCs (cASCs) from the adipose tissue of a canine and characterized the cASCs-EVs. Interestingly, we found that cASC-EVs improved AD-like dermatitis and markedly decreased the levels of serum IgE, ear thickness, inflammatory cytokines, and chemokines such as IL-4 and IFN-γ in a dose-dependent manner. Moreover, there was no systemic toxicity in single- or repeat-dose toxicity studies using ICR mice. In addition, we analyzed miRNA arrays from cASC-EVs using next-generation sequencing (NGS) to investigate the role of miRNAs in improving inflammatory responses. Collectively, our results suggest that cASC-EVs effectively attenuate AD by transporting anti-inflammatory miRNAs to atopic lesions alongside no toxicological findings, resulting in a promising cell-free therapeutic option for treating canine AD.
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