AdipoRon is a selective, orally active, synthetic

small-molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

adiponectin receptor 1 Adiponectin receptor 1 (AdipoR1) is a protein which in humans is encoded by the ''ADIPOR1'' gene. It is a member of the progestin and adipoQ receptor (PAQR) family, and is also known as PAQR1. Structure Similar to G protein-coupled receptors (GP ...

(AdipoR1) and

adiponectin receptor 2 Adiponectin receptor 2 (AdipoR2) is a protein which in humans is encoded by the ''ADIPOR2'' gene. It is a member of the progestin and adipoQ receptor (PAQR) family, and is also known as PAQR2. Structure Similar to G protein-coupled receptors (GPC ...

(AdipoR2) (K_d = 1.8 μM and 3.1 μM, respectively). It activates

AMPK AMPK may refer to: * AMP-activated protein kinase, an enzyme * (acetyl-CoA carboxylase) kinase In enzymology, a cetyl-CoA carboxylasekinase () is an enzyme that catalyzes the chemical reaction :ATP + cetyl-CoA carboxylase\rightleftharpoons AD ...

and PPARα

signaling In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The '' IEEE Transactions on Signal Processing' ...

and ameliorates

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...

dyslipidemia Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...

, and

glucose intolerance Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...

in ''db/db'' mice (an

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

for

type II diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

). Moreover, AdipoRon has been found to extend the lifespans of ''db/db'' mice fed a high-fat diet, as well as improve exercise endurance. The compound was discovered by Japanese researchers in 2013 via screening of a compound library, and is the first orally active, small-molecule agonist of the

adiponectin receptor The adiponectin receptors (AdipoRs) include the following two receptors, which are bound and activated by adiponectin: * Adiponectin receptor 1 (AdipoR1, PAQR1) * Adiponectin receptor 2 (AdipoR2, PAQR2) They are members of the progestin and adip ...

s to be identified. Adiponectin receptor agonists such as AdipoRon have attracted interest as potential therapies for obesity,

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...

non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...

, and a panoply of other conditions. In addition,

adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produce ...

has recently been elucidated to mediate the

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

, and

neurogenic In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...

effects of

physical exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...

. Dysregulation of adiponectin expression has also been implicated in the

pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and Stati ...

anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

eating disorder An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating ...

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

s, and various other

neuropsychiatric disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

s. Also, it has been determined that exercise improves

via activation of AdipoR1. As such, adiponectin receptor agonists are a highly interesting therapeutic target for a variety of different conditions. Moreover, it has been suggested they could potentially be used as a substitute for exercise to achieve similar physical and mental health benefits. In 2016, the University of Tokyo announced that it would launch an investigation into claims of fabrication of AdipoR1, AdipoR2, and AdipoRon identification data, as accused by an anonymous person/group called Ordinary_researchers.University of Tokyo to investigate data manipulation charges against six prominent research groups
ScienceInsider, Dennis Normile, Sep 20, 2016

References

Acetamides Adiponectin receptor agonists Anti-diabetic drugs Antidepressants Antiobesity drugs Piperidines {{nervous-system-drug-stub