Recent Updates on Obesity Treatments: Available Drugs and Future Directions. (15th June 2020)

• Record Type: Journal Article
• Authors: Dragano, Nathalia R.V.; Fernø, Johan; Diéguez, Carlos; López, Miguel; Milbank, Edward
• Is Part Of: Neuroscience. Volume 437(2020)
• Page Start: 215
• Page End: 239
• Publication Date: 2020-06-15
• Subjects: α-MSH Alpha-melanocyte-stimulating hormone -- 17β-HSD 17β-hydroxysteroid dehydrogenase -- 5-HT Hydroxytryptamine -- AgRP Agouti-related peptide -- AMPA/KA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/kainate -- AMPK AMP-activated protein kinase -- ARC Arcuate nucleus -- BAT Brown adipose tissue -- BMI Body mass index -- CD36/FATP-1 Cluster of differentiation/ Fatty acid transport protein 1 -- CerS1 Ceramide synthase 1 -- DIO Diet-induced obese -- DPP-IV Dipeptidyl peptidase IV -- E2 17β-estradiol -- EMA European Medicine Agency -- ER Endoplasmic reticulum -- FDA Food and Drug Administration -- FFAs Free fatty acids -- GCGR Glucagon receptor -- GCKR Glucokinase regulator -- GIP Glucose-dependent insulinotropic polypeptide -- GIPR GIP receptors -- GLP-1R Glucagon-like peptide-1 receptor -- GLUT4 Glucose transporter type 4 -- GRP78/BiP Glucose-regulated protein 78 kDa/binding immunoglobulin protein -- HDL High-density lipoprotein -- HFD High fat diet -- HR Hazard ratio -- IGF-1 Insulin-like growth factor-1 -- IKKβ/NF-κB Inhibitor of nuclear factor kappa-B kinase β/nuclear factor-kappa B -- IL-1β Interleukin-1β -- IL-6 Interleukin-6 -- IRS-1 and IRS-2 Insulin receptor substrates 1 and 2 -- JAK-STAT Janus kinase/signal transducer and activator of transcription -- JNK c-Jun N-terminal kinase -- LDL Low-density lipoprotein -- LHA Lateral hypothalamus -- MAPK Mitogen-activated protein kinase -- MBOAT7 Membrane bound O-acyltransferase domain-containing 7 -- MCP-1 Monocyte-chemoattractant protein-1 -- NAFLD Nonalcoholic fatty liver disease -- NASH Nonalcoholic steatohepatitis -- NEFAs Non-esterified fatty acids -- NO Nitric oxide -- NPY Neuropeptide Y -- OR Odds ratio -- PEPCK Enzyme phosphoenolpyruvate carboxykinase -- PI3K Phosphoinositide 3-kinase -- PKB Protein kinase B -- PNPLA3 Patatin-like phospholipase domain-containing protein 3 -- POMC Proopiomelanocortin -- PVH Paraventricular hypothalamic nucleus -- RBP4 Retinol-binding protein 4 -- RYGB Roux-en-Y gastric bypass -- SHBG Sex hormone-binding globulin -- SNS Sympathetic nervous system -- T2D Type II diabetes -- TH Thyroid hormone -- TM6SF2 Transmembrane 6 superfamily member 2 -- TNFα Tumor necrosis factor α -- TZD Thiazolidinedione -- UCP1 Uncoupling protein 1 -- VLDL Very low-density lipoprotein -- VMH Ventromedial nucleus of the hypothalamus -- WAT White adipose tissue -- WHO World Health Organization; obesity -- associated-pathologies -- pharmacotherapy -- polypharmacology; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.04.034
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The prevalence of obesity has risen dramatically worldwide over the last decades. Overweight and obesity are major risk factors for numerous comorbidities. Currently, bariatric surgery is the most effective way to induce body weight loss. The FDA-approved anti-obesity drugs are few and their efficiency remains limited. Promising pharmacotherapies targeting CNS and combining different mechanisms to induce body weight loss are in development. Abstract: In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. Currently, bariatric surgery is the most effective way to efficiently lower body mass. Although great improvements in terms of recovery and patient care were made in these surgical procedures, bariatric surgery remains an option for extreme forms of obesity and seems unable to tackle obesity pandemic expansion. Throughout the last century, numerous pharmacological strategies targeting either peripheral or central components of the energy balance regulatory system were designed to reduce body mass, some of them reaching sufficient levels of efficiency and safety. Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.