Pyrroloquinoline-quinone to reduce fat accumulation and ameliorate obesity progression

Abstract

Obesity is a major health concern worldwide, and its prevalence continues to increase in several countries. Pyrroloquinoline quinone (PQQ) is naturally found in some foods and is available as a dietary supplement in its disodium crystal form. The potential health benefits of PQQ have been studied, considering its antioxidant and anti-inflammatory properties. Furthermore, PQQ has been demonstrated to significantly influence the functions of mitochondria, the organelles responsible for energy production within cells, and their dysfunction is associated with various health conditions, including obesity complications. Here, we explore PQQ properties that can be exploited in obesity treatment and highlight the underlying molecular mechanisms. We review animal and cell culture studies demonstrating that PQQ is beneficial for reducing the accumulation of visceral and hepatic fat. In addition to inhibiting lipogenesis, PQQ can increase mitochondria number and function, leading to improved lipid metabolism. Besides diet-induced obesity, PQQ ameliorates programing obesity of the offspring through maternal supplementation and alters gut microbiota, which reduces obesity risk. In obesity progression, PQQ mitigates mitochondrial dysfunction and obesity-associated inflammation, resulting in the amelioration of the progression of obesity co-morbidities, including non-alcoholic fatty liver disease, chronic kidney disease, and Type 2 diabetes. Overall, PQQ has great potential as an anti-obesity and preventive agent for obesity-related complications. Although human studies are still lacking, further investigations to address obesity and associated disorders are still warranted.

Keywords: PQQ; fat; inflammation; lipogenesis; metabolic syndrome; mitochondria; obesity; pyrroloquinoline quinone.

FIGURE 1

PQQ in reducing fat accumulation and ameliorating obesity progression. (A) PQQ reduced visceral and hepatic fats in HFD-induced obese mice. Control mice have accumulated fat, especially visceral fat. The steatosis condition caused by fats building up in the liver was observed in control mice. The images were obtained and edited from our previous study (Mohamad Ishak et al., 2021). (B) PQQ action in reducing fat accumulation and improving obesity conditions. Fat accumulation occurs when excess energy, such as sugar (glucose), is converted into fatty acids via lipogenesis and stored in fat cells (adipose tissue) as triglycerides, leading to obesity. When necessary, fatty acids are metabolized through beta-oxidation (or fatty acid oxidation) in the mitochondria, and energy is produced in the form of adenosine triphosphate. PQQ attenuates fat accumulation by suppressing fatty acid synthesis (lipogenesis) and enhances beta-oxidation by boosting mitochondrial biogenesis. Mitochondrial dysfunction and inflammation occur during obesity progression. Mitochondrial dysfunction causes ROS accumulation and activates inflammatory pathways, releasing pro-inflammatory cytokines and inflammasomes. Inflammation further impairs mitochondrial function, creating a cycle of dysfunction and inflammation. When inflammation becomes chronic, it can lead to tissue damage and contribute to the development of insulin resistance. These events cause various health conditions, including NAFLD, type 2 diabetes, and CKD. With PQQ treatment, the enhancement of mitochondrial biogenesis mitigates mitochondrial dysfunction complications and its anti-inflammatory properties aid in resolving inflammation. Additionally, PQQ improved insulin resistance, and alleviates lipotoxicity in the fetal kidney and liver by decreasing ROS levels. The anti-obesity effects of PQQ have been shown to improve obesity complications. The microbiota Firmicutes/Bacteroidetes (F/B) ratio refers to the ratio of two major phyla of bacteria in the gut microbiome. Studies have shown that an increased F/B ratio is associated with obesity and other metabolic disorders. PQQ reversed F/B ratio in HFD animals and reduced inflammatory markers. The illustration was created with BioRender.com.