Molecular Mechanisms and Combinatorial Strategies in Anti-Obesity Therapeutics

Dear Colleagues,

The obesity epidemic and its associated complications increase the risk for type 2 diabetes, cardiovascular disease, cancer, depression, and COVID 19-associated hospitalizations. While the use of the adiposity hormone leptin as an anti-obesity therapy initially showed promise, subsequent studies demonstrated its inability to reliably elicit weight loss in humans with more common forms of obesity, a concept known as “leptin resistance”. While significant advances have been made in developing anti-obesity therapies that target glucagon-like peptide-receptor 1 (GLP-1R), these treatments often cause mild to moderate adverse gastrointestinal side effects, including abdominal pain, nausea and diarrhea. Multi-drug cocktails aim to reduce energy intake and/or stimulate energy expenditure at subthreshold dose or low-dose combinations and may be required to induce weight loss without the accompanying GI side effects.

This Special Issue, “Effect of Dietary and Pharmacological Interventions on Food Intake and Body Weight”, seeks to highlight findings on the pharmaceutical effects of obesity treatments in high-fat-diet-induced obese (DIO) and genetically obese rodent models. It focuses on novel combination treatment strategies that result in weight loss by reducing energy intake and/or increasing energy expenditure in DIO and genetically obese rodents. Furthermore, it identifies molecular mechanisms that contribute to these effects using cellular, molecular, biological, chemical and immunological approaches. It concludes by discussing current gaps, inconsistencies, and some of the ongoing challenges in this field to facilitate the adoption of dual- and triple-agonist-based therapeutics as a viable anti-obesity treatment strategy in rodent models without adverse side effects.

We welcome the submission of original research articles, mini reviews and reviews describing pre-clinical findings in rodent models in the following areas:

• The effects of novel monotherapies on energy intake and the control of body weight.
• The impact of novel combination therapies and dual and triple agonists as effective weight loss strategies in diet-induced obese rodent models and the molecular mechanisms that contribute to these effects.

Dr. James Ernest Blevins
Dr. Pawel K. Olszewski
Guest Editors

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