Obesity, classified as a disease since 1948 and recognized by the World Health Organization (WHO) as "abnormal or excessive fat accumulation that may impair health," has become a global epidemic. The prevalence of obesity continues to rise, with estimates suggesting that over one billion people worldwide will be affected by 2030. This increase poses a major public health issue, as obesity is a significant risk factor for chronic diseases, including diabetes, musculoskeletal disorders, cardiovascular diseases, and certain cancers.
The Challenge of Weight Management
Managing weight loss in individuals with overweight or obesity is a complex and multifaceted challenge. Various methods have been developed, including diets, pharmacotherapy, and lifestyle interventions, but a universal solution remains elusive. Moreover, many existing methods struggle to achieve long-term weight maintenance.
Helping overweight patients drop pounds is an ongoing battle for doctors. With over a third of Americans considered obese -- and either unwilling or unable to lose weight -- medical scientists and experts are after the holy grail: an easy, inexpensive solution to weight loss.
The Rise of Digital Technologies in Weight Loss Interventions
The introduction of new technologies has significantly impacted lifestyle choices and health. Smartphones and wearable devices have become ubiquitous, leading to both increased sedentary behavior and new opportunities for health promotion. Digital resources, such as activity trackers, mobile applications, and devices, can deliver messages and goals to motivate healthy behaviors, including physical activity and dietary changes.
The use of digital technologies may be useful to support weight-loss interventions for people with overweight or obesity. A systematic review of randomized controlled trials focused on digital-based technologies aimed at increasing physical activity for weight loss revealed that two-thirds of the studies reported significantly greater weight loss among electronic device users compared to controls. Many of these studies involved tailored or specialist-guided interventions.
Read also: Weight Loss Guide Andalusia, AL
Weight Loss Chip Technology: A Novel Approach
Researchers are exploring innovative technological solutions to combat obesity, including implantable microchips designed to curb appetite.
Intelligent Implantable Modulator
Researchers from the United Kingdom have developed a microchip, called an "intelligent implantable modulator," that can be implanted on a nerve to curb appetite. This small microchip models the neural signals responsible for appetite control. Measuring only several millimeters wide, the chip will attach to the vagus nerve in the abdominal cavity using cuff electrodes.
The vagus nerve is a primary communicator between the brain and digestive tract. The weight loss chip reads the reoccurring electrical and chemical signals of appetite produced in the nerve and sends a signal to the brain to suppress eating. In addition to communicating with the brain, the chip would also signal the same message ("resist the urge to eat!") to the intestines.
The researchers are claiming that the chip would be a more efficient -- and cheaper -- option than weight-loss surgery for severely overweight individuals. The research team already had developed a similar technology called MIMATE, which is currently being tested to help children with cerebral palsy and epileptic seizures. MIMATE reads chemical signals sent from the brain to an affected organ and then sends stimulating impulses to the organ. The main difference between MIMATE and the weight loss chip is that the newer device it doesn't send stimulating impulses.
Clinical Trials and Future Prospects
Animal testing for the weight loss chip will begin soon, followed by three years of clinical trials. The European Research Council has committed the equivalent of $9 million towards this project.
Read also: Beef jerky: A high-protein option for shedding pounds?
Implantable Brain Chip
Scientists have also developed tiny brain chips that could alter the activity of the brain area involved in experiencing pleasure from food. When reward anticipation is marked by stronger than normal delta waves, the RNS chip responds by triggering electrical stimulation to this area, resulting in reduced food intake.
The RNS was first approved by the US Food and Drug Administration (FDA) as an add-on treatment people with partial onset seizures. Before they could apply this technology to obesity, the scientists needed to identify an equivalent pattern of reward-anticipatory brain activity in humans. The human participants will have the chips implanted for at least 18 months, and the total duration of the trial will be five years. The aim of this research will be to test the safety and feasibility of the procedure.
The researchers emphasize that their aim is to help treat those with morbid obesity and not for casual weight reduction. Thus, the device should only be used in those with a body mass index (BMI) over 45 who have failed to lose weight even with advanced therapies like gastric bypass surgery or cognitive behavioral therapy.
Addressing the Challenges of Preclinical Testing
The development of new treatments, including weight loss interventions, faces significant challenges in preclinical testing. Many treatments that show promise in animal studies fail in clinical trials due to safety concerns or lack of efficacy in humans.
Tissue Chip Technology
To address the need for more predictive preclinical testing approaches, the National Institutes of Health (NIH) launched the Tissue Chip for Drug Screening program in 2012. This program aims to fund the development of tissue chips, miniature 3D platforms that accurately model the structure and function of human organs.
Read also: Inspiring Health Transformation
Tissue chips are tiny systems about the size of a USB stick consisting of human cells and microfluidic chambers capable of delivering nutrients and removing waste, embedded in transparent materials that allow real-time, longitudinal measurements to be taken. Tissue chips can be cultured with human cells derived from healthy and diseased donors in order to investigate the specific biological mechanisms of disease states.
In the coming years, tissue chip technologies may prove to be especially valuable in the study, diagnosis, and treatment of diseases in which an individual patient’s molecular pathology is important, such as rare diseases and cancer. The tissue chip with perhaps the most immediate demand is the liver chip, such as the one being developed by scientists at Emulate, due to its applications for testing the liver toxicity of drugs and other compounds found in consumer products.
Adipose-on-a-Chip Technology
Obatala Sciences has been granted an exclusive license from Harvard University to commercialize innovations that enable the study of human fat tissue in vitro. The licensed Harvard technology, an adipose-on-a-chip, provides a method of obtaining adult-size fat tissue cells for study in vitro and enables the testing of weight loss and cancer-targeting therapeutics without the need for testing in animals.
The adipose chips can respond to starvation and simulated meals, and they demonstrate key hormonal activity that is a hallmark of adipose as a functional organ.
Overcoming Limitations of Traditional Models
Traditional in vitro pharmaceutical studies have historically been limited by their inability to accurately simulate physiologic conditions. Adipose tissue is exceptionally reactive to the environment around it, as it dynamically stores and releases energy in response to hormonal and energetic cues.
The Importance of 3D Microenvironments
The majority of current obesity research has focused primarily on preclinical animal models in vivo and two-dimensional cell culture models in vitro. Neither of these generalized approaches is optimal due to interspecies variability, insufficient accuracy with respect to predicting human outcomes, and failure to recapitulate the three-dimensional (3D) microenvironment.
Human and murine cell lines and primary cultures are being combined with bioscaffolds to create functional 3D environments that are suitable for metabolically active adipose organoids in both static and perfusion bioreactor cultures. The development of these technologies will have considerable impact on the future pace of discovery for novel small molecules and biologics designed to prevent and treat metabolic syndrome and obesity in humans.
Simulating Multi-Organ Interactions
Perhaps the most significant issues associated with in vitro models come from their inability to simulate an environment with multiple compartments. This limits the utility of any model using adipose tissue as it is becoming increasingly accepted that adipose tissue has significant endocrine functionality necessary to maintain homeostasis. To create a better model capable of meeting these requirements, multiple organ systems, or outputs from multiple organ systems, must be simulated simultaneously.
The Gut-Immune Axis and Lab-on-Chip Technology
The gut-immune axis, with diet as a main regulator, has been identified as a possible role player in the onset and progression of metabolic diseases. Lab-on-chip technology offers an attractive new avenue to study gut-immune interactions.
While there has been progress in the development of “immuno-competent” intestinal lab-on-chip models, platforms which combine mechanical cues, longer-term co-culture of microbiota, and in vivo-like oxygen gradients, and include intestinal and immune cells are still lacking.
Metabolic Memory and Epigenetic Mechanisms
Strategies relying on behavioral and dietary changes for weight loss frequently only result in short-term WL and are susceptible to the ‘yo-yo’ effect, in which individuals regain weight over time. This recurrent pattern may be partially attributable to an (obesogenic) metabolic memory that persists even after notable WL or metabolic improvements.
Epigenetic mechanisms and modifications are essential for development, differentiation and identity maintenance of adipocytes in vitro and in vivo, but are also expected to be crucial contributors to the cellular memory of obesity.
Transcriptional Changes in Human Adipose Tissue
Single-nucleus RNA sequencing (snRNA-seq) of adipose tissue from individuals living with obesity before and after significant weight loss, as well as lean, obese and formerly obese mice, confirms the presence of retained transcriptional changes. Cell type-specific gene expression analysis revealed that many differentially expressed genes (DEGs) in obese individuals were also deregulated after weight loss. Transcriptional deregulation during obesity was most pronounced in adipocytes, adipocyte progenitor cells (APCs) and endothelial cells.
Transcriptional Obesogenic Memory in Mice
Mouse epididymal adipose tissue (epiAT) cellular changes throughout obesity and weight loss have been examined using snRNA-seq. Macrophage cell number in epiAT was higher in obese conditions and was not fully normalized after weight loss. Resident macrophages in control mice primarily consisted of perivascular macrophages and non-perivascular macrophages, while during obesity lipid-associated macrophage (LAM) and non-perivascular macrophage cell numbers increased in the epiAT, altering the macrophage population composition persistently.
Across cell types many DEGs from the obesity time point remained deregulated after weight loss. Gene set enrichment analysis (GSEA) of retained DEGs showed persistent upregulation of genes related to lysosome activity, apoptosis and other inflammatory pathways, indicating endoplasmic reticulum and cellular stress.
Vibrating Ingestible Capsules for Satiety
MIT engineers have developed an ingestible capsule that vibrates in the stomach, simulating fullness by activating stretch receptors, which in animal studies reduced food intake by about 40%.
When the stomach becomes distended, specialized cells called mechanoreceptors sense that stretching and send signals to the brain via the vagus nerve. As a result, the brain stimulates the production of insulin, as well as hormones such as C-peptide, Pyy, and GLP-1. All of these hormones work together to help people digest their food, feel full, and stop eating.
In animals who were given this pill 20 minutes before eating, the researchers found that this treatment not only stimulated the release of hormones that signal satiety, but also reduced the animals’ food intake by about 40 percent.
Clinical Trials and Future Prospects
The researchers now plan to explore ways to scale up the manufacturing of the capsules, which could enable clinical trials in humans.