-
Physiological Research Sep 2020Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food... (Review)
Review
Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved.
Topics: Animals; Anti-Obesity Agents; Genome-Wide Association Study; Humans; Molecular Targeted Therapy; Mutation; Obesity; Receptor, Melanocortin, Type 4; alpha-MSH
PubMed: 33094623
DOI: 10.33549/physiolres.934512 -
Current Opinion in Clinical Nutrition... Mar 2022During critical illness, several neuroendocrine, inflammatory, immune, adipokine, and gastrointestinal tract hormone pathways are activated; some of which are more... (Review)
Review
PURPOSE OF REVIEW
During critical illness, several neuroendocrine, inflammatory, immune, adipokine, and gastrointestinal tract hormone pathways are activated; some of which are more intensified among obese compared with nonobese patients. Nutrition support may mitigate some of these effects. Nutrition priorities in obese critically ill patients include screening for nutritional risk, estimation of energy and protein requirement, and provision of macronutrients and micronutrients.
RECENT FINDINGS
Estimation of energy requirement in obese critically ill patients is challenging because of variations in body composition among obese patients and absence of reliable predictive equations for energy expenditure. Whereas hypocaloric nutrition with high protein has been advocated in obese critically ill patients, supporting data are scarce. Recent studies did not show differences in outcomes between hypocaloric and eucaloric nutrition, except for better glycemic control. Sarcopenia is common among obese patients, and the provision of increased protein intake has been suggested to mitigate catabolic changes especially after the acute phase of critical illness. However, high-quality data on high protein intake in these patients are lacking. Micronutrient deficiencies among obese critically ill patients are common but the role of their routine supplementation requires further study.
SUMMARY
An individualized approach for nutritional support may be needed for obese critically ill patients but high-quality evidence is lacking. Future studies should focus on nutrition priorities in this population, with efficient and adequately powered studies.
Topics: Critical Illness; Dietary Proteins; Energy Intake; Humans; Nutritional Requirements; Nutritional Support; Obesity
PubMed: 34930871
DOI: 10.1097/MCO.0000000000000803 -
Journal of Biomedical Science Feb 2022Obesity is nowadays considered a pandemic which prevalence's has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease... (Review)
Review
Obesity is nowadays considered a pandemic which prevalence's has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity's association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.
Topics: Adipocytes; Adipokines; Adipose Tissue; Humans; Immunotherapy; Inflammation; Neoplasms; Obesity; Tumor Microenvironment
PubMed: 35164764
DOI: 10.1186/s12929-022-00796-0 -
Expert Review of Gastroenterology &... 2023Obesity is considered a poor lifestyle choice. 'Obesity' is not a sufficient definition for patients, any more than 'cancer' or 'arthritis' would be. A major obstacle is... (Review)
Review
INTRODUCTION
Obesity is considered a poor lifestyle choice. 'Obesity' is not a sufficient definition for patients, any more than 'cancer' or 'arthritis' would be. A major obstacle is the lack of understanding of pathogenesis. The disease of obesity is considered homogenous, while response to treatment is thought of as heterogeneous. This can change if pathogenesis, risk profiles for complications, and treatment responses are viewed within the context of obesity consisting of several subsets of disease.
AREAS COVERED
The European Union-funded Innovative Medicine Initiative project Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy is part of a momentum shift. Operational variables are being used to develop tests and therapies which may allow the prediction of risk of obesities and the prediction of response to obesity treatments. However, changing stakeholder perspectives on obesity may require more than high-quality data and analysis.
EXPERT OPINION
For patients to benefit, clinicians need to integrate evidence-based treatments and payers need to reimburse the management of the disease of obesity. This will generate commercial opportunities for industry. We need to involve stakeholders (patients, clinicians, regulators, payer, patient organisations) to create a shared value for mutual gain.
Topics: Humans; Obesity; Forecasting; Life Style
PubMed: 37791820
DOI: 10.1080/17474124.2023.2264783 -
Cancer Letters Jan 2022The epidemiological correlation between obesity and cancer is well characterized, but the biological mechanisms which regulate tumor development and response to therapy... (Review)
Review
The epidemiological correlation between obesity and cancer is well characterized, but the biological mechanisms which regulate tumor development and response to therapy in obese cancer patients remain unclear. The tumor microenvironment plays an important role in protecting cancer cells by altering the delivery of anticancer therapy to the tumor tissue, reducing the efficacy of treatment. Obese tumor microenvironment provides additional benefits to the survival of tumor cells against anticancer therapies by altering the extracellular matrix composition, angiogenesis processes and the immune cells profile. Nanotechnology, and in particular gold nanoparticles, are being researched as a theranostic strategy for cancer treatment due to their ability to sensitize cancer cells to radiation and photodynamic therapy, enhance delivery of drugs to tumor cells, and in diagnostic applications. Adipose tissue and the obese tumor microenvironment may alter the activity of nanotherapeutics. In this article, we reviewed the current state of our understanding about the mechanisms by which the obese tumor microenvironment may alter the delivery and efficacy of anti-cancer treatments, and why the use of gold nanoparticles may represent an interesting strategy for cancer treatment in the obesity setting.
Topics: Adipose Tissue; Drug Delivery Systems; Extracellular Matrix; Gold; Humans; Metal Nanoparticles; Neoplasms; Obesity; Tumor Microenvironment
PubMed: 34662546
DOI: 10.1016/j.canlet.2021.10.017 -
International Journal of Molecular... Apr 2021Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus,... (Review)
Review
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
Topics: Anti-Obesity Agents; Antioxidants; Humans; Obesity; Resveratrol
PubMed: 33921991
DOI: 10.3390/ijms22094362 -
Techniques in Vascular and... Mar 2020Obesity poses a significant health care concern in the United States, with 39.8% of adults being classified as obese. Several different methods have been introduced to... (Review)
Review
Obesity poses a significant health care concern in the United States, with 39.8% of adults being classified as obese. Several different methods have been introduced to combat obesity, from medical therapy to surgical options. Bariatric surgery has been demonstrated to be superior to medical therapy alone for weight loss in obese patients. Despite this information, only about 1% of eligible patients undergo bariatric surgery per year. The reason for this treatment gap is multifactorial, but patient apprehension to undergo surgery is a major driving force. Many patients perceive bariatric surgery as dangerous, and believe that living with their current weight is safer than undergoing surgery. To combat this treatment gap, endoscopic therapies have been developed to reach more patients in a less invasive way. This article will review endoscopic treatment options currently available and approved by the Food and Drug Administration, as well as other treatment modalities that are currently in development.
Topics: Appetite Regulation; Bariatric Surgery; Endoscopy, Gastrointestinal; Equipment Design; Feeding Behavior; Humans; Obesity; Patient Acceptance of Health Care; Patient Safety; Risk Assessment; Risk Factors; Treatment Outcome; Weight Loss
PubMed: 32192635
DOI: 10.1016/j.tvir.2020.100655 -
The Journals of Gerontology. Series A,... Sep 2019Substantial evidence suggests that individuals born to overweight and obese parents suffer detrimental health consequences that dramatically decrease healthy aging. The...
Substantial evidence suggests that individuals born to overweight and obese parents suffer detrimental health consequences that dramatically decrease healthy aging. The number of obese individuals worldwide now exceeds the number of under- and malnourished individuals. This obesity epidemic is responsible for approximately 4 million deaths worldwide each year, and predisposes sufferers to a range of age-related diseases such as cardiovascular diseases, and metabolic syndrome. Additionally, obesity is associated with an accelerated onset of age-related ailments, such as cancers and inflammation. The importance of dietary interventions to reduce the incidence of obesity is magnified by emerging evidence that parental physiology can predispose future generations to poor health outcomes. Characterizing and understanding these effects, and how they are mediated, is important if we are to continue to drive improvements to population health. In this article, we synthesize evidence for the intergenerational and transgenerational phenotypic effects of parental obesity. We concentrate on how the fruit fly Drosophila melanogaster can be used as a model to study these effects. Fruit flies are highly tractable, and their conserved nutrient signaling and metabolic pathways make them an ideal model for studying nutritional effects on metabolic, reproductive, and aging phenotypes.
Topics: Aging; Animals; Drosophila melanogaster; Family Health; Feeding Behavior; Intergenerational Relations; Models, Animal; Obesity; Phenotype
PubMed: 31231757
DOI: 10.1093/gerona/glz154 -
Heart Failure Clinics Jul 2020Obesity is very common in patients with heart failure with preserved ejection fraction (HFpEF). Obesity and increased adiposity have multiple adverse effects on the... (Review)
Review
Obesity is very common in patients with heart failure with preserved ejection fraction (HFpEF). Obesity and increased adiposity have multiple adverse effects on the cardiovascular system, including hemodynamic, inflammatory, mechanical, and neurohormonal effects. Obesity and increased adiposity may be a promising target for therapy in HFpEF. This review summarizes the current understanding of the pathophysiology of obesity-related HFpEF, diagnostic evaluation of HFpEF among obese patients with dyspnea, and potential therapeutic options for the HFpEF obesity phenotype.
Topics: Disease Management; Heart Failure; Hemodynamics; Humans; Obesity; Stroke Volume
PubMed: 32503758
DOI: 10.1016/j.hfc.2020.02.004 -
Current Pharmaceutical Design 2020The number of individuals with obesity is growing worldwide and this is a worrying trend, as obesity has shown to cause pathophysiological changes, which result in the... (Review)
Review
BACKGROUND
The number of individuals with obesity is growing worldwide and this is a worrying trend, as obesity has shown to cause pathophysiological changes, which result in the emergence of comorbidities such as cardiovascular disease, diabetes mellitus type 2 and cancer. In addition, cognitive performance may be compromised by immunometabolic deregulation of obesity. Although in more critical cases, the use of medications is recommended, a physically active lifestyle is one of the main foundations for health maintenance, making physical training an important tool to reduce the harmful effects of excessive fat accumulation.
AIM
The purpose of this review of the literature is to present the impact of immunometabolic alterations on cognitive function in individuals with obesity, and the role of exercise training as a non-pharmacological approach to improve the inflammatory profile, energy metabolism and neuroplasticity in obesity.
METHOD
An overview of the etiology and pathophysiology of obesity to establish a possible link with cognitive performance in obese individuals, with the executive function being one of the most affected cognitive components. In addition, the brain-derived neurotrophic factor (BDNF) profile and its impact on cognition in obese individuals are discussed. Lastly, studies showing regular resistance and/or aerobic training, which may be able to improve the pathophysiological condition and cognitive performance through the improvement of the inflammatory profile, decreased insulin resistance and higher BDNF production are discussed.
CONCLUSION
Exercise training is essential for reestablishment and maintenance of health by increasing energy expenditure, insulin resistance reduction, anti-inflammatory proteins and neurotrophin production corroborating to upregulation of body function.
Topics: Cognition; Exercise Therapy; Humans; Insulin Resistance; Obesity
PubMed: 31942854
DOI: 10.2174/1381612826666200114102524