| Leptin agonism . | |||
|---|---|---|---|
| Background . | Features . | Clinical outcome . | Reference . |
| Mouse | |||
| ob/ob | Obesity, excessive food intake, infertile | Decrease of body weight, food intake, serum insulin and glucose level; normalization of body fat percentage; increase of total activity and lean mass | Pelleymounter et al., 1995; Halaas et al., 1995 |
| db/db | Obesity, excessive food intake, infertile, hyperglycemia | Not responding | Halaas et al., 1995; Farooqi et al., 1999 |
| Human | |||
| Congenital leptin deficiency | Early-onset obesity, hyperphagia, alteration of the immune function | Weight loss, decreased basal metabolic rate, increased physical activity level, increased basal and stimulated serum gonadotropin concentration | Farooqi et al., 1999 |
| Acquired leptin deficiency (lipodystrophy) | Generalized lack of body fat, insulin resistance, hypertriglyceridemia, polycystic ovary syndrome | Decreased average triglyceride level, glycosylated hemoglobin, and plasma glucose level; improved metabolic control | Oral et al., 2002; Santos and Cortés, 2020 |
| Mutation in the LEPR gene | Early-onset obesity, hyperphagia, impaired pubertal development, reduced secretion of growth hormone and thyrotropin | Not responding (other possible therapies: bariatric surgery or setmelanotide treatment) | Clément et al., 1998 |
| General obesity | Dysmetabolic syndrome, leptin resistance | Not responding | |
| Leptin antagonism (rodent studies only) | |||
| Pathology | Antagonizing molecule | Clinical outcome | Reference |
| Inflammation and Autoimmunity | |||
| Chronic liver fibrosis | Mutated leptin | Reduced IFN-γ levels, attenuated liver fibrosis, improved survival | Elinav et al., 2009 |
| Chronic experimental colitis | Mutated leptin | Reduced systemic and mucosal pro-inflammatory cytokines and clinical severity; increased T reg cell number | Singh et al., 2013 |
| EAE | Neutralizing leptin antibody or soluble LepR chimera | Slowed disease progression, reduced relapses, FOXP3+CD4+ T cell induction and pro-inflammatory T cell proliferation blockade | De Rosa et al., 2006 |
| SLE | Neutralizing leptin antibody | Hampered pro-inflammatory Th17 cell response | Yu et al., 2013 |
| Cancer | |||
| Aggressive breast cancer | LepR antagonist | Increased average survival time | Otvos et al., 2011a |
| Acute myelocytic leukemia | Neutralizing LepR monoclonal antibody | Decreased leukemic cell number and angiogenesis within the bone marrow | Iversen et al., 2002 |
| Leptin agonism . | |||
|---|---|---|---|
| Background . | Features . | Clinical outcome . | Reference . |
| Mouse | |||
| ob/ob | Obesity, excessive food intake, infertile | Decrease of body weight, food intake, serum insulin and glucose level; normalization of body fat percentage; increase of total activity and lean mass | Pelleymounter et al., 1995; Halaas et al., 1995 |
| db/db | Obesity, excessive food intake, infertile, hyperglycemia | Not responding | Halaas et al., 1995; Farooqi et al., 1999 |
| Human | |||
| Congenital leptin deficiency | Early-onset obesity, hyperphagia, alteration of the immune function | Weight loss, decreased basal metabolic rate, increased physical activity level, increased basal and stimulated serum gonadotropin concentration | Farooqi et al., 1999 |
| Acquired leptin deficiency (lipodystrophy) | Generalized lack of body fat, insulin resistance, hypertriglyceridemia, polycystic ovary syndrome | Decreased average triglyceride level, glycosylated hemoglobin, and plasma glucose level; improved metabolic control | Oral et al., 2002; Santos and Cortés, 2020 |
| Mutation in the LEPR gene | Early-onset obesity, hyperphagia, impaired pubertal development, reduced secretion of growth hormone and thyrotropin | Not responding (other possible therapies: bariatric surgery or setmelanotide treatment) | Clément et al., 1998 |
| General obesity | Dysmetabolic syndrome, leptin resistance | Not responding | |
| Leptin antagonism (rodent studies only) | |||
| Pathology | Antagonizing molecule | Clinical outcome | Reference |
| Inflammation and Autoimmunity | |||
| Chronic liver fibrosis | Mutated leptin | Reduced IFN-γ levels, attenuated liver fibrosis, improved survival | Elinav et al., 2009 |
| Chronic experimental colitis | Mutated leptin | Reduced systemic and mucosal pro-inflammatory cytokines and clinical severity; increased T reg cell number | Singh et al., 2013 |
| EAE | Neutralizing leptin antibody or soluble LepR chimera | Slowed disease progression, reduced relapses, FOXP3+CD4+ T cell induction and pro-inflammatory T cell proliferation blockade | De Rosa et al., 2006 |
| SLE | Neutralizing leptin antibody | Hampered pro-inflammatory Th17 cell response | Yu et al., 2013 |
| Cancer | |||
| Aggressive breast cancer | LepR antagonist | Increased average survival time | Otvos et al., 2011a |
| Acute myelocytic leukemia | Neutralizing LepR monoclonal antibody | Decreased leukemic cell number and angiogenesis within the bone marrow | Iversen et al., 2002 |