Synthetic thyroid hormone may reduce cholesterol and treat obesity.

Synthetic thyroid hormone may reduce cholesterol and treat obesity.

A Nanogel to Reverse Obesity and Lower Cholesterol Levels

Introduction

Being overweight and having high cholesterol are common issues that many people face worldwide. Both conditions can increase the risk of developing other serious health problems, such as cardiovascular disease and diabetes. However, researchers from the University of Massachusetts Amherst have recently made a groundbreaking discovery. They have developed a nanogel-based carrier that delivers a synthetic thyroid hormone-mimicking drug directly to the liver. This liver-targeted drug system has shown promising results in mice, effectively helping them return to a healthy weight and lower their cholesterol levels.

The Global Impact of Obesity and High Cholesterol

Obesity affects more than 1 billion people around the world. This condition occurs when a person has an excessive amount of weight or body fat for their height and age. Additionally, approximately 28.5 million people globally struggle with high cholesterol, a condition characterized by an excess of cholesterol in the body. High cholesterol can lead to the buildup of cholesterol in the arteries, impairing proper blood flow. Individuals who are obese and/or have high cholesterol face a higher risk of developing cardiovascular disease, high blood pressure, diabetes, and certain types of cancer.

Nanogel-based Carrier for Targeted Delivery

The researchers from the University of Massachusetts Amherst designed a nanogel-based carrier to deliver a synthetic thyroid hormone-mimicking drug specifically to the liver. The nanogels were engineered to have an inherent propensity for homing in on the liver, as metabolic disorders often require targeting the hepatocytes in this organ. By decorating the nanogels with additional chemical functionalities, the researchers ensured their preferential homing to the liver and uptake by hepatocytes.

The thyromimetic drug used in this study targets the thyroid hormone receptor beta, which is predominantly found in the liver. Activating this receptor triggers various physiological responses, including fatty acid oxidation and the reverse cholesterol pathway (RCT). These responses are believed to contribute to the observed weight loss and cholesterol reduction. However, further research is necessary to confirm this hypothesis.

Overcoming Historical Challenges

Thyroid hormone mimics have previously been tested as cholesterol-lowering agents and are currently undergoing clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). However, there have been two major challenges associated with these mimics – their bioavailability and potential off-target effects on other organs. The University of Massachusetts Amherst researchers sought to overcome these challenges by combining a potent thyromimetic with their nanogel carrier.

The nanogel carrier provides a concentrated and targeted delivery of the drug to the liver, minimizing systemic exposure and potential toxicity. By integrating a highly effective thyromimetic with this carrier system, the researchers aimed to achieve optimal cholesterol-lowering activity while ensuring safety and efficacy.

Impressive Results in Mouse Model

To assess the efficacy of the liver-targeted drug system, the researchers conducted a study using mice. They fed one group of mice a high-fat, high-sugar, and high-cholesterol diet for 10 weeks, resulting in a doubling of their weight. Simultaneously, they maintained a control group of mice on a healthy diet during the same period.

The obese mice were administered the thyromimetic drug in the nanogel carrier via daily intraperitoneal injections for five weeks. At the end of this period, the researchers made remarkable observations. Despite the continuation of the high-fat diet, the obese mice achieved weight loss and returned to their previous weight. Additionally, these mice experienced decreases in their cholesterol levels and improvements in liver inflammation.

Dr. S. Thai Thayumanavan, the lead author of this study, expressed his surprise and excitement at the impact this drug had on body weight reduction. Unlike traditional thyroid hormone mimics, their drug showed no adverse side effects, making it safe for potential human use.

Implications and Future Research

Dr. Rigved Tadwalkar, a board-certified cardiologist at Providence Saint John’s Health Center, commended the study for its potential breakthrough in targeting organ-specific treatment. He emphasized the need for further research and cautioned against prematurely extrapolating results from animal models to human clinical trials. The transition from preclinical studies to human trials is a complex process that requires careful consideration and verification.

The Importance of the Liver and Its Impact on Health

The liver, the body’s largest solid organ, is responsible for over 500 essential functions. Located in the upper right area of the abdomen, the liver plays a vital role in filtering the blood, breaking down toxins, producing bile for digestion, metabolizing nutrients, regulating blood sugar, storing vitamins and minerals, and protecting the body from infection.

Obesity and high cholesterol can have a profound impact on liver health. Fatty liver disease, often associated with obesity, can worsen due to high cholesterol levels. Inflammation of the liver caused by high cholesterol increases the risk of developing various liver diseases and damage. Conversely, an inflamed liver may disrupt bile production, leading to elevated cholesterol levels in the body.

Tips for Maintaining a Healthy Liver

Dr. Mir Ali, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center, emphasized the importance of maintaining a healthy weight to prevent liver damage in individuals with obesity. Losing weight and avoiding toxins, such as alcohol, can play a crucial role in the recovery and protection of the liver.

While the recent nanogel-based drug delivery study holds promise, further research and human clinical trials are needed to fully understand its efficacy and potential benefits for individuals struggling with obesity and high cholesterol.

In conclusion, the development of a nanogel-based carrier for targeted drug delivery to the liver represents a significant advancement in addressing obesity and high cholesterol. The liver-specific delivery of a thyromimetic drug has shown impressive results for weight loss and the reduction of cholesterol levels. While the study is still in its early stages, it offers hope for more effective and safer treatment options in the future.