Description:
Background
Leptin is a hormone produced by adipocytes and is elevated in obesity. The congenital lack of leptin results in obesity and the metabolism field widely accepts the concept. Upon cloning of the leptin gene, the original hope was that leptin would act as a break for further food intake and a trigger to increase energy expenditure. The hope was that the injection of recombinant leptin would act as an effective weight loss mechanism. However, these hopes were quickly disappointed, since obese individuals have high leptin levels, but these individual are leptin resistant. Not even the injection of very high leptin levels can overcome this resistance.
Technology Highlights
Inventors at the UTHealth Institute for Molecular Medicine and UT Southwestern Medical Center have discovered a series of novel and unique observations, in which a decremental reduction in circulating leptin levels initiates an unexpected and significant improvement in several parameters of energy balance and glucose homeostasis. This system-wide response includes significant weight loss, reduced food-intake and increased energy expenditure; all indicative of enhanced leptin sensitization. A battery of monoclonal antibodies against human and mouse leptin were degenerated, showing strong binding affinities to human leptin and significant neutralizing activity in vivo. More importantly, treatment of high-fat diet (HFD)-fed mice with neutralizing antibodies reduces body-weight gain and confirmed findings in mice with a genetic knock-down of leptin. The anti-leptin antibodies have the potential to provide an effective treatment for obesity where patients have a high level of leptin but are resistant to the conventional leptin treatment.
Possible Features and Benefits of this Technology
· Methods and compositions for treating obesity and/or diabetes
· Pharmacological interventions that are associated with weight gain, such as the treatment with anti-psychotics or glucocorticoids, both of which result in leptin induction and rapid weight gain, resulting in insulin resistance. Neutralizing leptin antibodies have significant potential to prevent weight gain.
· Applications in cancer research in which the cancer phenotype critically depends on leptin signaling, such as acute lymphoblastic leukemia and breast cancer
Related Publications:
· Zhao S, Kusminski CM, Elmquist JK, Scherer PE. 2020. “Leptin: Less is More” Diabetes, in press
· Zhao S, Zhu Y, Schultz RD, Li N, He Z, Zhang Z, Caron A, Zhu Q, Sun K, Xiong W, Deng H, Sun J, Deng Y, Kim M, Lee CE, Gordillo R, Liu T, Odle AK, Childs GW, Zhang N, Kusminski CM, Elmquist JK, Williams KW, An Z and PE Scherer. 2019. “Partial Leptin Reduction as an Effective Weight Loss Strategy” Cell Metabolism, 30; (4)706-719
UTHealth Ref. No.: 2018-0031
Inventors: Dr. Zhiqiang An and Dr. Ningyan Zhang at UTHealth; Dr. Phil Scherer at UT Southwestern Medical Center
Patent Status: PCT applications PCT/US2019/037223 and PCT/US2019/037236
License Available: world-wide, exclusive or non-exclusive