Why Pet Obesity is More Than a Weight Problem
Pet obesity has reached critical levels, with around 1 in 5 to 1 in 4 of our cats and dogs estimated to be clinically obese, and between 40% to 60% considered overweight.
Being overweight or obese is a driver for osteoarthritis, diabetes, cancer, and cardiovascular disease in our companions. For example, overweight or obese dogs are 2.3 times more likely to be diagnosed with osteoarthritis and obese cats are 2–4 times more likely to develop diabetes. Excess weight can also lead to a reduced quality of life and a shorter life span, by up to 2.5 years in dogs and 1.5 years in cats.
K161, modulates fat cell function and induces WAT "beiging"
Obesity is a complex, multifactorial disease influenced by genetics and environment. In most mammals, including cats, dogs and humans, two primary types of adipose “fat” tissues exist, each with its own special function: brown adipose tissue (BAT) and white adipose tissue (WAT). BAT contains thermogenic adipocytes which are responsible for heat generation in the body and is quickly burnt off. In contrast, WAT adipocytes store excess fat and is associated with obesity. A third cell type, beige adipocytes, are a type of fat cell found in WAT which shares the heat generating features of BAT. Inducing WAT “beiging” i.e., transforming energy-storing white fat cells into beige energy-burning fat cells has emerged as a promising anti-obesity strategy. K161 modulates fat cell function and induces WAT "beiging".
K161, reduces chronic inflammation and enhances insulin sensitivity
When a pet (or human) gains weight, their white adipocytes don't just increase in number; they grow significantly in size (hypertrophy) and this “overcrowding” and the resulting oxygen deprivation (hypoxia) induces a stress reaction within the fat tissue, with release of pro-inflammatory cytokines (e.g., IFN-γ and IL-12), recruitment and polarization of pro-inflammatory immune cells (e.g. M1 macrophages) and the establishment of a chronic low-grade inflammation.
SHIP1 and SHIP2 are phosphatases that inhibit intracellular signaling. SHIP1 is predominantly active in immune cells (e.g. inhibits immune activation) while SHIP2 is more widespread (e.g. can prevent the fat cells from responding to insulin, worsening the metabolic stress). K161 inhibits both SHIP1/SHIP2 signaling, thereby promoting the secretion of anti-inflammatory cytokines (e.g., IL-4 and IL-13) from eosinophils and Th2 lymphocytes such as ILC2, restoring macrophage polarization toward the anti-inflammatory (M2) phenotype, reducing inflammation and thereby "resetting" the fat tissue to its lean, anti-inflammatory state.
K161 administration resulted in weight loss of ~20%
In preclinical small animal studies, it was shown that animals receiving K161 lose weight, an outcome that was not dependent on appetite suppression or enhanced physical activity; instead K161 limits inflammation and improves metabolism to promote leanness. Administration of K161 resulted in:
i) Reduced adiposity, particularly in visceral fat depots. Mice maintained on a high-fat diet (HFD) showed a mean weight loss of almost 20% during the 4-week treatment period, which was significantly greater than the net-zero weight loss seen in the vehicle (H2O) group.
ii) Improved glucose tolerance and insulin sensitivity
iii) Protection against diet-induced obesity, even in the absence of caloric restriction
iv) Immune modulation, including increased activity of regulatory immune cells in adipose tissue.