Impact of A Cargo-Less Liposomal Formulation on Dietary Obesity-Related Metabolic Disorders in Mice.
Varsha KomallaBehjat SheikholeslamiGerard LiBishwajit BokshiYik Lung ChanAlison UngBrian Gregory George OliverHui ChenMehra HaghiPublished in: International journal of molecular sciences (2020)
Current therapeutic options for obesity often require pharmacological intervention with dietary restrictions. Obesity is associated with underlying inflammation due to increased tissue macrophage infiltration, and recent evidence shows that inflammation can drive obesity, creating a feed forward mechanism. Therefore, targeting obesity-induced macrophage infiltration may be an effective way of treating obesity. Here, we developed cargo-less liposomes (UTS-001) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC (synthetic phosphatidylcholine) as a single-agent to manage weight gain and related glucose disorders due to high fat diet (HFD) consumption in mice. UTS-001 displayed potent immunomodulatory properties, including reducing resident macrophage number in both fat and liver, downregulating liver markers involved in gluconeogenesis, and increasing marker involved in thermogenesis. As a result, UTS-001 significantly enhanced systemic glucose tolerance in vivo and insulin-stimulated cellular glucose uptake in vitro, as well as reducing fat accumulation upon ad libitum HFD consumption in mice. UTS-001 targets tissue residence macrophages to suppress tissue inflammation during HFD-induced obesity, resulting in improved weight control and glucose metabolism. Thus, UTS-001 represents a promising therapeutic strategy for body weight management and glycaemic control.
Keyphrases
- weight gain
- high fat diet induced
- insulin resistance
- high fat diet
- adipose tissue
- weight loss
- type diabetes
- metabolic syndrome
- body mass index
- birth weight
- body weight
- oxidative stress
- skeletal muscle
- randomized controlled trial
- drug induced
- drug delivery
- blood pressure
- high glucose
- physical activity
- diabetic rats
- patient safety