Obesity Targets

Target Search

Background

What is Obesity?

Obesity is a global health problem that involves the excessive accumulation of fat in the body, resulting in weight that is beyond a healthy range. Obesity has been linked to several chronic diseases, including cardiovascular disease, type 2 diabetes, some types of cancer, sleep apnea, and arthritis. Obesity may also affect mental health, such as increasing the risk of anxiety and depression. Treatment for obesity often includes lifestyle changes such as a healthy diet and regular exercise. Medication and surgery are also options to treat obesity in some cases, but these methods are often used as an adjunct to lifestyle changes.

Modern lifestyles, such as high-calorie diets, sedentary lifestyles and lack of exercise, are major factors contributing to rising obesity rates. Environmental factors, such as food advertising and availability, can also influence an individual's dietary choices and activity levels. Genetic factors play a role in the development of obesity, and certain gene variants may increase an individual's risk of developing obesity.

Obesity is on the rise worldwide and has become a serious public health problem. Among them, childhood obesity is a serious public health problem, which not only affects children's current health and growth, but also may increase the risk of multiple chronic diseases in adulthood. Government and public health agencies are taking steps to tackle obesity, including promoting healthy diets, increasing physical activity facilities and limiting advertising of unhealthy foods.

Causes of Obesity

Obesity is a chronic disease, not easy to overcome, easy to relapse. The reason of its occurrence and development may be the result of system dynamic factors, environmental driving factors and personal risk factors. While weight is influenced by genetics, behavior, metabolism, and hormones, obesity occurs when calories are consumed in excess of those burned through daily activities and exercise. These excess calories are stored in your body as fat. Other factors such as hormonal changes in women, taking medications, gut microbiota, sleep and stress can also contribute to obesity.

Obesity Symptoms

The international definition of obesity is based on body mass index (BMI). So what bmi is obese? According to the World Health Organization (WHO), BMI for adults is classified as follows: A BMI of less than 18.5 is considered underweight. A BMI between 18.5 and 24.9 is considered normal weight. A person with a BMI between 25 and 29.9 is overweight.
A BMI of 30 or above is considered obese. The WHO classifies obesity into three levels: Class 1: BMI between 30 and 34.9. Class 2 obesity: BMI between 35 and 39.9. Class 3 obesity: A BMI of 40 or greater.

In addition to being overweight, it can also cause other symptoms. Increased respiratory burden due to weight gain. Obesity can lead to sleep apnea, which manifests as snoring during sleep. Obesity leads to fat lines, which are caused by rapid stretching of the skin. Increased social and psychological problems such as shame, guilt, social isolation, and depression.
What's more serious, there are quite a few complications. Such as:

• Heart disease and stroke. Obese people are more likely to have high blood pressure and unhealthy cholesterol levels, which are risk factors for heart disease and stroke.
• Type 2 diabetes. Obesity can affect the way the body uses insulin to control blood sugar levels. This increases the risk of insulin resistance and diabetes.
• Certain cancers. Obesity may increase the risk of uterine, cervical, endometrial, ovarian, breast, colon, rectal, esophageal, liver, gallbladder, pancreatic, kidney, and prostate cancers.
• Osteoarthritis. Obesity increases stress on weight-bearing joints. Obesity also promotes inflammation, including swelling, pain and the feeling of heat in the body. These factors may lead to complications such as osteoarthritis.
• Fatty liver disease. Obesity increases the risk of developing fatty liver disease, which is a condition caused by excessive fat deposits in the liver. In some cases, obesity can lead to severe liver damage, known as cirrhosis.

Obesity Treatment

Preventing obesity is easier than treating it. Once weight is gained, the body will resist weight loss. For example, you feel hungrier when you diet and you burn less energy when you rest. Starting with some daily habits, obesity can be treated to some extent.

• Eat healthier foods (high in fiber, low in sugar)
• Reduce the amount of food you put on your plate so you're not tempted to overeat
• Avoid high-calorie beverages such as soda, juice, or alcohol
• Get more exercise and activity (e.g., take the stairs instead of the elevator, or walk instead of driving or taking the bus)
• Attending group meetings and talking to others who are trying to lose or manage their weight may help maintain healthy eating and exercise habits.

While for patients who need to lose significant amounts of weight, medication or surgery may be used.

Case Study

Case Study 1: Recombinant Dog GLP1R Protein (GLP1R-01D)

Loureirin B (LB) is a naturally occurring substance sourced from Sanguis draconis and is known to have blood sugar-lowering properties. To explore its potential role in diabetes management, molecular docking was utilized to model the interaction between LB and various targets, with glucagon-like peptide-1 receptor (GLP-1R) showing the most promising outcomes. Subsequently, spectroscopic and surface plasmon resonance (SPR) techniques were employed to confirm the interaction between LB and GLP-1R. The significance of GLP-1R was further validated through experiments where its expression was suppressed using siRNA in Ins-1 cells, leading to a diminished insulin secretion effect from LB. These findings indicate that LB enhances insulin release from Ins-1 cells via GLP-1R. Consequently, considering LB as a prodrug presents a promising strategy for developing non-peptide GLP-1R agonists.

Fig1. Stern–Volmer curves of GLP‐1R fluorescence quenched LB. (Yanting Ding, 2021)

Case Study 2: Recombinant Human PTPN1 protein (PTPN1-31256TH)

Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition. In addition, the compound activity varied depending on vendor source. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5.

Fig2. An in vitro phosphatase assay shows RR601 inhibits PTP1B. (Robert D Bongard, 2017)

Case Study 3: Recombinant Human CNR1 Protein

Endocrine therapy offers a promising approach for treating endometrial cancer (EC) while preserving fertility, yet the challenge of progesterone resistance remains a significant obstacle. Analysis of The Cancer Genome Atlas (TCGA) database revealed a strong negative correlation between CNR1 expression and both overall survival (OS) and relapse-free survival (RFS) in EC patients. To delve into the role of CNR1 in progesterone resistance and to uncover potential molecular mechanisms, the researchers developed stable progesterone-resistant cell lines (IshikawaPR) through the adaptation of standard Ishikawa cancer cells to progesterone. They assessed the differences in CNR1 levels between the two cell lines using a variety of techniques, including MTT, RT-PCR, Western blot, and immunofluorescence. Subsequently, they utilized lentiviruses carrying CNR1-knockdown constructs with GV248 as the vector to transfect IshikawaPR cells and observed related phenotypes. The findings indicate that when CNR1 was knocked down in IshikawaPR cells, there was a notable reduction in their proliferative capacity and migratory ability, along with an enhanced sensitivity to progesterone. Additionally, the knockdown of CNR1 led to decreased expression and activation of ERK and NFκB pathways.

Fig3. Survival analysis of CNR1 different expression group. (Fei Ding, 2021)

Obesity is a global health problem that involves the excessive accumulation of fat in the body, resulting in weight that is beyond a healthy range. According to the World Health Organization (WHO), obesity is usually measured by body mass index (BMI), which is weight in kilograms divided by the square of height in meters. In general, a BMI of 30 or more is considered obese. It is important to note that BMI is only an estimate of body fat content, and it does not fully distinguish between muscle and fat tissue, so it may not be accurate enough in some cases. In clinical practice, obesity and its associated health risks may also be assessed in conjunction with other measures such as waist circumference.
Obesity not only affects physical health, but can also have a negative impact on psychological and social well-being. Treating obesity requires an integrated approach, often a combination of multiple strategies, and requires the active involvement and long-term commitment of the patient. Importantly, the treatment plan should be developed by a medical professional and tailored to the patient's specific circumstances.