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Obesity

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Description: Obesity is a medical condition characterized by the excessive accumulation of body fat that presents a risk to health.
Type: Obesity can have a multifactorial genetic transmission. It is influenced by a combination of multiple genes and environmental factors, rather than being transmitted through a simple Mendelian inheritance pattern. Specific genetic variations, such as those in the FTO gene, can increase susceptibility to obesity, but lifestyle and environmental factors play significant roles as well.
Signs And Symptoms: Signs and symptoms of obesity include:

1. **Excess Body Fat**: Visible increase in body fat, particularly around the waist.
2. **Body Mass Index (BMI)**: A BMI of 30 or higher.
3. **Breathlessness**: Difficulty breathing, especially with exertion.
4. **Sweating**: Increased sweating unrelated to temperature or exertion.
5. **Snoring**: Chronic snoring or sleep apnea.
6. **Inability to Perform Activities**: Difficulty with physical activities or mobility.
7. **Joint and Back Pain**: Pain in weight-bearing joints and lower back.
8. **Low Self-Esteem**: Negative self-image and low confidence.
9. **Skin Issues**: Skin problems such as rashes or infections in skin folds.
10. **Fatigue**: Persistent tiredness and fatigue.
Prognosis: Prognosis for obesity varies based on several factors including the individual's overall health, the presence of comorbid conditions, and the degree of obesity. With appropriate interventions such as lifestyle changes, medical treatments, and, in some cases, surgical procedures, many individuals can achieve significant weight loss and improvement in health. However, without effective management, obesity is associated with an increased risk of several serious health problems including cardiovascular disease, diabetes, certain cancers, and decreased life expectancy. Regular follow-ups and a multidisciplinary approach are often required to manage obesity effectively.
Onset: Onset: Obesity can develop gradually over time, often beginning in childhood or adolescence but can occur at any age. The development of obesity is influenced by a combination of genetic, environmental, behavioral, and metabolic factors.
Prevalence: Prevalence: Obesity is a global health issue affecting adults and children. It varies by region, but recent estimates indicate that about 39% of adults worldwide are overweight, and 13% are obese, based on Body Mass Index (BMI) data from the World Health Organization (WHO). The prevalence is higher in high-income countries but is increasing rapidly in low- and middle-income countries. In the United States, around 42% of adults and 19% of children and adolescents are considered obese.
Epidemiology: See or edit source data.

In earlier historical periods obesity was rare and achievable only by a small elite, although already recognised as a problem for health. But as prosperity increased in the Early Modern period, it affected increasingly larger groups of the population. Prior to the 1970s, obesity was a relatively rare condition even in the wealthiest of nations, and when it did exist it tended to occur among the wealthy. Then, a confluence of events started to change the human condition. The average BMI of populations in first-world countries started to increase, and consequently there was a rapid increase in the proportion of people overweight and obese.In 1997, the WHO formally recognized obesity as a global epidemic. As of 2008, the WHO estimates that at least 500 million adults (greater than 10%) are obese, with higher rates among women than men. The global prevalence of obesity more than doubled between 1980 and 2014. In 2014, more than 600 million adults were obese, equal to about 13 percent of the world's adult population. The percentage of adults affected in the United States as of 2015–2016 is about 39.6% overall (37.9% of males and 41.1% of females). In 2000, the World Health Organization (WHO) stated that overweight and obesity were replacing more traditional public health concerns such as undernutrition and infectious diseases as one of the most significant cause of poor health.The rate of obesity also increases with age at least up to 50 or 60 years old: 5 and severe obesity in the United States, Australia, and Canada is increasing faster than the overall rate of obesity. The OECD has projected an increase in obesity rates until at least 2030, especially in the United States, Mexico and England with rates reaching 47%, 39% and 35%, respectively.Once considered a problem only of high-income countries, obesity rates are rising worldwide and affecting both the developed and developing world. These increases have been felt most dramatically in urban settings.Sex- and gender-based differences also influence the prevalence of obesity. Globally there are more obese women than men, but the numbers differ depending on how obesity is measured.
Intractability: Obesity is often considered a complex and challenging condition to treat, but it is not intractable. Effective management typically requires a multifaceted approach, including dietary changes, increased physical activity, behavioral therapy, and, in some cases, medication or surgery. Success varies depending on individual circumstances, commitment, and access to appropriate resources and support.
Disease Severity: For obesity:

- Disease Severity: Varies significantly. It can range from mild to severe, with potential complications including type 2 diabetes, cardiovascular disease, certain cancers, and decreased quality of life.
- NAN: Not applicable (Assume it refers to "not a number" and not relevant for disease context).
Healthcare Professionals: Disease Ontology ID - DOID:9970
Pathophysiology: Two distinct but related processes are considered to be involved in the development of obesity: sustained positive energy balance (energy intake exceeding energy expenditure) and the resetting of the body weight "set point" at an increased value. The second process explains why finding effective obesity treatments has been difficult. While the underlying biology of this process still remains uncertain, research is beginning to clarify the mechanisms.At a biological level, there are many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until the leptin gene was discovered in 1994 by J. M. Friedman's laboratory. While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.
Carrier Status: Obesity is not typically characterized by a "carrier status" as it is not a single-gene disorder. Instead, obesity is a complex condition influenced by multiple genetic and environmental factors. Genetic predisposition to obesity can involve variations in multiple genes, but these do not typically follow a simple carrier model. Factors such as diet, physical activity, and metabolism also play significant roles in the development and management of obesity.
Mechanism: Obesity is a complex disease characterized by excessive accumulation of body fat. This condition arises from a combination of genetic, environmental, and behavioral factors.

**Mechanism:**
1. **Energy Imbalance**: Obesity typically results from an imbalance between calorie intake and energy expenditure. When caloric intake exceeds the body's energy needs over an extended period, the surplus energy is stored as fat in adipose tissues.
2. **Endocrine Factors**: Hormones such as insulin, leptin, and ghrelin play critical roles in regulating appetite, metabolism, and fat storage. Dysregulation of these hormones can contribute to obesity.

**Molecular Mechanisms:**
1. **Adipogenesis**: This involves the formation of new fat cells (adipocytes) from precursor cells. Key transcription factors such as PPARγ (Peroxisome proliferator-activated receptor gamma) and C/EBPα (CCAAT/enhancer-binding protein alpha) drive the differentiation of pre-adipocytes into mature adipocytes.
2. **Lipid Metabolism**: Enzymes such as lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) are crucial in the storage and mobilization of triglycerides within adipocytes.
3. **Leptin Signaling**: Produced by adipocytes, leptin regulates appetite and energy balance by signaling the hypothalamus in the brain. In obesity, leptin resistance may occur, impairing the satiety signal and leading to increased food intake and weight gain.
4. **Insulin Signaling**: Insulin promotes glucose uptake and lipid synthesis in adipose tissues. Obesity often leads to insulin resistance, a condition where cells become less responsive to insulin, resulting in higher blood glucose levels and further fat accumulation.
5. **Inflammation**: Obesity is associated with chronic low-grade inflammation. Adipose tissue produces inflammatory cytokines such as TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6), which can interfere with insulin signaling and contribute to metabolic dysregulation.
6. **Gut Microbiota**: The composition of gut bacteria can influence energy harvest from the diet and inflammatory status, both of which are implicated in obesity.
7. **Genetic Factors**: Various genes have been associated with obesity, including those affecting appetite regulation (e.g., MC4R - melanocortin 4 receptor) and metabolism (e.g., FTO - fat mass and obesity-associated gene).

Understanding these mechanisms offers pathways for potential therapeutic interventions to treat or prevent obesity.
Treatment: The treatment for obesity typically includes a combination of lifestyle changes, medical interventions, and sometimes surgical procedures. Key components of obesity treatment are:

1. **Dietary Changes**: Adopting a balanced, low-calorie diet with a focus on whole foods, such as fruits, vegetables, whole grains, and lean proteins. Reducing intake of high-sugar and high-fat foods is essential.

2. **Exercise**: Regular physical activity, such as aerobic exercises (walking, jogging, swimming) and strength training, helps in weight loss and improves overall health.

3. **Behavioral Therapy**: Counseling or therapy to identify and change unhealthy eating and activity habits. Support groups and weight management programs can also be beneficial.

4. **Medications**: Prescription medications may be used to help reduce appetite or increase feelings of fullness. These should always be used under the guidance of a healthcare provider.

5. **Surgery**: In cases of severe obesity or when other treatments have not been successful, bariatric surgery, such as gastric bypass or sleeve gastrectomy, may be considered.

Ongoing monitoring and support from healthcare providers are crucial to address the chronic nature of obesity and to manage its associated health risks, such as diabetes, heart disease, and hypertension.
Compassionate Use Treatment: For obesity, compassionate use treatment may involve the use of medications or therapies that have not yet received regulatory approval but show potential benefits for severe cases where other treatments have failed. Experimental treatments can include novel drugs or surgical techniques currently being evaluated in clinical trials.

Off-label treatments might include medications approved for other conditions but found to aid in weight loss. Examples include:

1. **Metformin** - Primarily used for type 2 diabetes, sometimes utilized to control weight gain, particularly linked to antipsychotic medications.

2. **Topiramate** - Originally an anticonvulsant, has been prescribed off-label for weight loss due to its appetite-suppressing properties.

3. **Liraglutide** - A GLP-1 receptor agonist approved for diabetes that also has weight loss benefits; high-dose formulations are specifically approved for obesity.

Experimental treatments in clinical trials might include new pharmacological agents, bariatric devices, gene therapy, or microbiome modifications.

For any treatment, especially those off-label or experimental, professional medical advice and monitoring are crucial.
Lifestyle Recommendations: ### Lifestyle Recommendations for Obesity:

1. **Healthy Diet**:
- Focus on a balanced diet with a variety of fruits, vegetables, whole grains, lean proteins, and healthy fats.
- Limit intake of sugary beverages, processed foods, and high-fat, high-sugar snacks.
- Practice portion control to avoid overeating.

2. **Regular Physical Activity**:
- Aim for at least 150 minutes of moderate-intensity aerobic activity (e.g., brisk walking) or 75 minutes of vigorous-intensity activity (e.g., running) per week, along with muscle-strengthening activities on 2 or more days a week.
- Incorporate physical activities into daily routines, such as walking or cycling to work, using stairs instead of elevators.

3. **Behavioral Changes**:
- Set realistic weight-loss goals and track progress.
- Keep a food diary to monitor eating habits.
- Establish regular mealtimes and avoid skipping meals.

4. **Sleep and Stress Management**:
- Ensure adequate sleep, aiming for 7-9 hours per night.
- Practice stress-reducing techniques such as meditation, yoga, or deep-breathing exercises.

5. **Avoid Sedentary Behavior**:
- Reduce screen time, including TV and computer usage.
- Take regular breaks to stand up and move around if you have a sedentary job.

6. **Seek Professional Support**:
- Consult healthcare providers for personalized advice.
- Consider joining a weight loss group or seeking counselling.

Implementing and maintaining these lifestyle changes can significantly contribute to weight loss and overall health improvement for individuals dealing with obesity.
Medication: Since the introduction of medicines for the management of obesity in the 1930s, many compounds have been tried. Most of them reduce body weight by small amounts, and several of them are no longer marketed for obesity because of their side effects. Out of 25 anti-obesity medications withdrawn from the market between 1964 and 2009, 23 acted by altering the functions of chemical neurotransmitters in the brain. The most common side effects of these drugs that led to withdrawals were mental disturbances, cardiac side effects, and drug abuse or drug dependence. Deaths were reportedly associated with seven products.Five medications beneficial for long-term use are: orlistat, lorcaserin, liraglutide, phentermine–topiramate, and naltrexone–bupropion. They result in weight loss after one year ranged from 3.0 to 6.7 kg (6.6-14.8 lbs) over placebo. Orlistat, liraglutide, and naltrexone–bupropion are available in both the United States and Europe, phentermine–topiramate is available only in the United States. European regulatory authorities rejected lorcaserin and phentermine-topiramate, in part because of associations of heart valve problems with lorcaserin and more general heart and blood vessel problems with phentermine–topiramate. Lorcaserin was available in the United States and then removed from the market in 2020 due to its association with cancer. Orlistat use is associated with high rates of gastrointestinal side effects and concerns have been raised about negative effects on the kidneys. There is no information on how these drugs affect longer-term complications of obesity such as cardiovascular disease or death; however, liraglutide, when used for type 2 diabetes, does reduce cardiovascular events.In 2019 a systematic review compared the effects on weight of various doses of fluoxetine (60 mg/d, 40 mg/d, 20 mg/d, 10 mg/d) in obese adults. When compared to placebo, all dosages of fluoxetine appeared to contribute to weight loss but lead to increased risk of experiencing side effects such as dizziness, drowsiness, fatigue, insomnia and nausea during period of treatment. However, these conclusions were from low certainty evidence. When comparing, in the same review, the effects of fluoxetine on weight of obese adults, to other anti-obesity agents, omega-3 gel and not receiving a treatment, the authors could not reach conclusive results due to poor quality of evidence.Among antipsychotic drugs for treating schizophrenia clozapine is the most effective, but it also has the highest risk of causing the metabolic syndrome, of which obesity is the main feature. For people who gain weight because of clozapine, taking metformin may reportedly improve three of the five components of the metabolic syndrome: waist circumference, fasting glucose, and fasting triglycerides.
Repurposable Drugs: For obesity, repurposable drugs include:

1. **Metformin**: Originally for type 2 diabetes, it can help with weight loss and improving insulin resistance.
2. **Liraglutide**: Initially for managing type 2 diabetes, it is also used for chronic weight management.
3. **Topiramate**: An anticonvulsant, it has shown weight loss effects, often in combination with other medications.

"Nan" doesn't have an obvious correlation in the context of obesity and repurposable drugs. If you meant something else, please clarify.
Metabolites: Obesity is associated with alterations in various metabolites, including glucose, lipids, and amino acids. Key metabolite changes often observed in obesity include elevated levels of glucose, free fatty acids, branched-chain amino acids (BCAAs like leucine, isoleucine, and valine), and inflammatory markers such as ceramides and acylcarnitines. These metabolic alterations contribute to the development of insulin resistance and other obesity-related complications.
Nutraceuticals: Nutraceuticals for obesity often include bioactive compounds like green tea extract, conjugated linoleic acid (CLA), and garcinia cambogia. These substances can potentially help in weight management by enhancing metabolism, reducing fat absorption, or suppressing appetite. However, their efficacy and safety can vary, and they should be used in conjunction with diet and exercise.

Nanotechnology in obesity treatment involves the development of nanoparticles for targeted drug delivery systems. These systems can potentially enhance the efficiency of anti-obesity drugs, reduce side effects, and provide controlled release of therapeutic agents. Research in this area is ongoing to improve treatment outcomes.
Peptides: In the context of obesity, peptides have gained attention for their role in regulating appetite, metabolism, and energy balance. For example, glucagon-like peptide-1 (GLP-1) is an incretin hormone that promotes insulin secretion, inhibits glucagon release, and slows gastric emptying, which can help reduce food intake and body weight. GLP-1 receptor agonists, such as liraglutide, are used as treatments for obesity.

Nano (nanotechnology) approaches are being explored to enhance the delivery and efficacy of obesity treatments. Nanoparticles can be used to improve the bioavailability and stability of drugs, target specific tissues, and reduce side effects by controlling the release profiles. This can potentially provide more effective and targeted obesity therapies.