Advantages of Adipokines in Developing Anti-obesity Therapies

Traditional anti-obesity approaches such as dieting, exercise, and even some pharmacological approaches typically focus on treating symptoms or reducing calorie intake without addressing the underlying biological mechanisms that lead to obesity. Adipokines are cell signaling proteins produced by adipose tissue that are involved in a variety of processes including energy and appetite regulation, lipid and glucose metabolism, insulin sensitivity, angiogenesis, inflammation, and more. Protheragen targets specific adipokines to develop therapies to correct the imbalance of these pathways in obesity, thereby achieving more effective and lasting weight loss and metabolic improvements. In addition, therapies targeting adipokines address obesity-related complications such as type 2 diabetes and cardiovascular disease by restoring metabolic homeostasis. We leverage the regulatory function of adipokines to develop new drugs for our clients, providing a holistic solution for obesity and its associated health risks.

Fig.1 White adipose tissue expansion in obesity. (Longo, et al., 2019)

Unlocking Adipokine Potential: Developing Anti-obesity Therapies!

Adipokines such as leptin, adiponectin, resistin, and visfatin play key roles in regulating metabolic processes, inflammation, and insulin sensitivity. Therapeutics such as small molecule drugs are designed to mimic or inhibit the effects of these adipokines, thereby altering metabolic pathways to combat obesity. We develop potential Anti-obesity Therapies targeting different adipokines, including Small Molecule Drugs, Gene Therapy, Antibody Therapy, combination therapy, etc.

Anti-obesity Therapy Development Targeting Multiple Adipokines

Fibroblast Growth Factor-21 (FGF-21): FGF-21 is a promising target for anti-obesity therapy due to its important role in regulating metabolism, insulin sensitivity, and energy expenditure. The FGF-21 analog PF-05231023 has been reported to reduce body weight and improve lipid profile in obese patients. Our strategy includes the development of FGF-21 analogs, small molecule FGF-21 activators, and gene therapy. FGF-21 analogs are designed to extend its half-life and enhance its biological activity by mimicking the beneficial effects of FGF-21. Small molecule FGF-21 activators are designed to upregulate endogenous production of FGF-21 or enhance its signaling pathways. Our gene therapy strategy modifies the FGF-21 gene to increase its expression in vivo.

Fig.2 FGF21 gene therapy. (Jimenez, et al., 2018)

FGF-19: FGF-19 is a hormone produced in the ileum in response to bile acid absorption, and its activation results in enhanced glycogen synthesis, increased fatty acid oxidation, and inhibition of bile acid synthesis. Our therapeutic development focuses on exploiting these metabolic benefits to design FGF-19 analogs and mimetics. They retain the metabolic benefits of native FGF-19 with improved stability and bioavailability. A non-mitogenic FGF-19 variant, NGM282, has been reported to be effective and safe in clinical studies.

Leptin: Leptin is a hormone produced by adipose tissue that helps suppress food intake and promotes energy expenditure. We help clients design leptin analogs or potentiators that effectively activate hypothalamic leptin receptors. We develop combination therapies that pair leptin with other drugs that enhance leptin signaling or reduce inflammation and other factors that contribute to leptin resistance.

Adiponectin: To maintain the protective effects of adiponectin against obesity and prevent the development of type II diabetes and cardiovascular disease, our strategy focuses on restoring the increased secretion of related adipokines in adipose tissue. First, developing small molecule agonists that activate adiponectin receptors to mimic the effects of this hormone. Second, using gene therapy to increase adiponectin expression in adipose tissue.

Resistin: Our targeted therapies are developed in the form of small molecule inhibitors and monoclonal antibodies that specifically bind to resistin, thereby neutralizing its effects or disrupting its interaction with the receptor. In addition, we also use gene silencing technologies such as small interfering RNA (siRNA) and antisense oligonucleotides to downregulate resistin expression in adipose tissue.

In addition, we also target adipokines such as chemerin, vaspin, visfatin, bone morphogenetic protein 7 (BMP-7), and tumor necrosis factor-alpha (TNF-α) to develop innovative therapies to combat obesity.

Preclinical Studies of Anti-obesity Therapies

We help clients analyze and evaluate the preclinical efficacy and Safety of potential therapies, including molecular and cellular studies to understand the mechanism of action, Obesity Model Studies to evaluate the efficacy of treatment and identify any adverse reactions, and Pharmacokinetic and Pharmacodynamic Studies to determine the appropriate dose and route of administration.

Workflow

Applications

• Develop effective gene therapies using gene editing technology to enhance or inhibit specific adipokine genes in adipose tissue.
• Develop monoclonal antibodies against specific adipokines to neutralize their effects or prevent their degradation.
• Use a multi-target approach to combine adipokine modulators with other anti-obesity drugs, develop combination therapies, and combine lifestyle interventions such as diet and exercise to improve overall metabolic outcomes.
• Develop dietary supplements or functional foods that modulate adipokine activity. For example, specific nutrients that increase adiponectin levels or reduce resistin levels.

Advantages

• Adipokines include a variety of molecules such as leptin, adiponectin, resistin, etc., each of which has a unique role in metabolism. We target specific molecules to develop anti-obesity therapies.
• We design effective treatment strategies to target multiple adipokines, which may produce synergistic effects and enhance therapeutic effects.
• We develop effective innovative drugs based on adipokines, such as monoclonal antibodies, peptides or recombinant proteins, and small molecule regulators.
• With expertise in endocrinology, molecular biology, pharmacology, and bioinformatics, we help clients develop comprehensive and effective treatment strategies.

Our Services

Publication Data

Frequently Asked Questions

How do adipokine-targeting drugs work?

Drugs targeting adipokines work by regulating the signaling pathways of adipokines. Adipokines are bioactive peptides or proteins secreted by adipose tissue that play a key role in metabolic processes such as appetite regulation, insulin sensitivity, inflammation, and energy expenditure. These drugs balance the body's adipokines, such as adiponectin and resistin to reduce weight, improve metabolic health, and alleviate obesity-related complications.

What are the advantages of targeting adipokines over traditional weight-loss methods?

Traditional weight loss interventions typically involve lifestyle changes such as diet and exercise, or bariatric surgery, which may not be acceptable or effective for everyone. In contrast, drugs targeting adipokines aim to modulate biochemical pathways that influence fat storage, metabolism, and appetite at the molecular level. More effective and lasting weight loss is achieved by addressing the root causes of obesity. In addition, such therapies are used in conjunction with lifestyle changes to increase their effectiveness or provide an alternative for people who have difficulty using traditional weight loss methods. By directly altering the biochemical signals involved in fat regulation, adipokine-targeted therapies offer a more targeted and less invasive solution to obesity.

At Protheragen, we help clients around the world develop effective anti-obesity therapies by targeting adipokines with our cutting-edge R&D pipeline and advanced technologies. These novel therapies more precisely impact pathways that control hunger, satiety, and fat storage. Please feel free to contact us to learn more about our development strategies for targeting adipokines and unlocking a healthier future for people struggling with weight-related issues.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

• Targeting Tumor Necrosis Factor-alpha (TNF-α) for Developing Anti-Obesity Therapeutics