Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024.

Background: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. Methods: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. Results: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. Conclusions: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.

Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024.

BACKGROUND: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. METHODS: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. RESULTS: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. CONCLUSIONS: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.

Obesity medicine as a subspecialty and United States certification - A review.

Background: Certification of obesity medicine for physicians in the United States occurs mainly via the American Board of Obesity Medicine (ABOM). Obesity medicine is not recognized as a subspecialty by the American Board of Medical Specialties (ABMS) or the American Osteopathic Association (AOA). This review examines the value of specialization, status of current ABOM Diplomates, governing bodies involved in ABMS/AOA Board Certification, and the advantages and disadvantages of an ABMS/AOA recognized obesity medicine subspecialty. Methods: Data for this review were derived from PubMed and appliable websites. Content was driven by the expertise, insights, and perspectives of the authors. Results: The existing ABOM obesity medicine certification process has resulted in a dramatic increase in the number of Obesity Medicine Diplomates. If ABMS/AOA were to recognize obesity medicine as a subspecialty under an existing ABMS Member Board, then Obesity Medicine would achieve a status like other ABMS recognized subspecialities. However, the transition of ABOM Diplomates to ABMS recognized subspecialists may affect the kinds and the number of physicians having an acknowledged focus on obesity medicine care. Among transition issues to consider include: (1) How many ABMS Member Boards would oversee Obesity Medicine as a subspecialty and which physicians would be eligible? (2) Would current ABOM Diplomates be required to complete an Obesity Medicine Fellowship? If not, then what would be the process for a current ABOM Diplomate to transition to an ABMS-recognized Obesity Medicine subspecialist (i.e., "grandfathering criteria")? and (3) According to the ABMS, do enough Obesity Medicine Fellowship programs exist to recognize Obesity Medicine as a subspecialty? Conclusions: Decisions regarding a transition to an ABMS recognized Obesity Medicine Subspecialty versus retention of the current ABOM Diplomate Certification should consider which best facilitates medical access and care to patients with obesity, and which best helps obesity medicine clinicians be recognized for their expertise.

Stress, psychiatric disease, and obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: Previous Obesity Medicine Association (OMA) Clinical Practice Statements (CPS) included topics such as behavior modification, motivational interviewing, and eating disorders, as well as the effect of concomitant medications on weight gain/reduction (i.e., including psychiatric medications). This OMA CPS provides clinicians a more focused overview of stress and psychiatric disease as they relate to obesity. Methods: The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: Topics in this CPS include the relationship between psychological stress and obesity, including both acute and chronic stress. Additionally, this CPS describes the neurobiological pathways regarding stress and addiction-like eating behavior and explores the relationship between psychiatric disease and obesity, with an overview of psychiatric medications and their potential effects on weight gain and weight reduction. Conclusions: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on stress and psychiatric disease is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of obesity. Knowledge of stress, addiction-like eating behavior, psychiatric disease, and effects of psychiatric medications on body weight may improve the care obesity medicine clinicians provide to their patients with obesity.

Corrigendum to "Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022" [Obes Pillars 2 (2022) 100018].

[This corrects the article DOI: 10.1016/j.obpill.2022.100018.].

Obesity history, physical exam, laboratory, body composition, and energy expenditure: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on History, Physical Exam, Body Composition and Energy Expenditure is intended to provide clinicians an overview of the clinical and diagnostic evaluation of patients with pre-obesity/obesity. Methods: The scientific information for this CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: This CPS outlines important components of medical, dietary, and physical activity history as well as physical exams, with a focus on specific aspects unique to managing patients with pre-obesity or obesity. Patients with pre-obesity/obesity benefit from the same preventive care and general laboratory testing as those without an increase in body fat. In addition, patients with pre-obesity/obesity may benefit from adiposity-specific diagnostic testing - both generally and individually - according to patient presentation and clinical judgment. Body composition testing, such as dual energy x-ray absorptiometry, bioelectrical impedance, and other measures, each have their own advantages and disadvantages. Some patients in clinical research, and perhaps even clinical practice, may benefit from an assessment of energy expenditure. This can be achieved by several methods including direct calorimetry, indirect calorimetry, doubly labeled water, or estimated by equations. Finally, a unifying theme regarding the etiology of pre-obesity/obesity and effectiveness of treatments of obesity centers on the role of biologic and behavior efficiencies and inefficiencies, with efficiencies more often associated with increases in fat mass and inefficiencies more often associated with decreases in fat mass. Conclusion: The Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on History, Physical Exam, Body Composition and Energy Expenditure is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of pre-obesity/obesity.

Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This "Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association Clinical Practice Statement 2022" is intended to provide clinicians an overview of Food and Drug Administration (FDA) approved anti-obesity medications and investigational anti-obesity agents in development. Methods: The scientific information for this Clinical Practice Statement (CPS) is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: This CPS describes pharmacokinetic principles applicable to those with obesity, and discusses the efficacy and safety of anti-obesity medications [e.g., phentermine, semaglutide, liraglutide, phentermine/topiramate, naltrexone/bupropion, and orlistat, as well as non-systemic superabsorbent oral hydrogel particles (which is technically classified as a medical device)]. Other medications discussed include setmelanotide, metreleptin, and lisdexamfetamine dimesylate. Data regarding the use of combination anti-obesity pharmacotherapy, as well as use of anti-obesity pharmacotherapy after bariatric surgery are limited; however, published data support such approaches. Finally, this CPS discusses investigational anti-obesity medications, with an emphasis on the mechanisms of action and summary of available clinical trial data regarding tirzepatide. Conclusion: This "Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association Clinical Practice Statement 2022" is one of a series of OMA CPSs designed to assist clinicians in the care of patients with pre-obesity/obesity.

Behavior, motivational interviewing, eating disorders, and obesity management technologies: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of "Behavior, Motivational Interviewing, Eating Disorders, and Obesity Management Technologies." Methods: The scientific information for this CPS is based upon published scientific citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: This CPS outlines important components of behavior, motivational interviewing, eating disorders, and obesity management technologies as they relate to pre-obesity and obesity. Topics include eating behavior disorder evaluation, the motivations behind eating and physical activity behaviors (including underlying neurophysiology, eating disorders, environmental factors, and personal prioritization), motivational interviewing techniques, and technologies that may assist with pre-obesity/obesity management. Conclusions: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on "Behavior, Motivational Interviewing, Eating Disorders, and Obesity Management Technologies" is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of pre-obesity/obesity. Implementation of appropriate clinical practices in these areas may improve the health of patients, especially those with adverse fat mass and adiposopathic metabolic consequences.

Nutrition and physical activity: An Obesity Medicine Association (OMA) Clinical Practice Statement 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on Nutrition and Physical Activity provides clinicians an overview of nutrition and physical activity principles applicable to the care of patients with increased body fat, especially those with adverse fat mass and adiposopathic metabolic consequences. Methods: The scientific information and clinical guidance is based upon referenced evidence and derived from the clinical perspectives of the authors. Results: This OMA CPS on Nutrition and Physical Activity provides basic clinical information regarding carbohydrates, proteins, fats (including trans fats, saturated fats, polyunsaturated fats, and monounsaturated fats), general principles of healthful nutrition, nutritional factors associated with improved health outcomes, and food labels. Included are the clinical implications of isocaloric substitution of refined carbohydrates with saturated fats and vice-versa, as well as definitions of low-calorie, very low-calorie, carbohydrate-restricted, and fat-restricted dietary intakes. Specific dietary plans discussed include carbohydrate-restricted diets, fat-restricted diets, very low-calorie diets, the Mediterranean diet, Therapeutic Lifestyle diet, Dietary Approaches to Stop Hypertension (DASH), ketogenic (modified Atkins) diet, Ornish diet, Paleo diet, vegetarian or vegan diet (whole food/plant-based), intermittent fasting/time restricted feeding, and commercial diet programs. This clinical practice statement also examines the health benefits of physical activity and provides practical pre-exercise medical evaluation guidance as well as suggestions regarding types and recommended amounts of dynamic (aerobic) training, resistance (anaerobic) training, leisure time physical activity, and non-exercise activity thermogenesis (NEAT). Additional guidance is provided regarding muscle physiology, exercise prescription, metabolic equivalent tasks (METS), and methods to track physical activity progress. Conclusion: This Obesity Medicine Association Clinical Practice Statement on Nutrition and Physical Activity provides clinicians an overview of nutrition and physical activity. Implementation of appropriate nutrition and physical activity in patients with pre-obesity and/or obesity may improve the health of patients, especially those with adverse fat mass and adiposopathic metabolic consequences.

Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster.

Rapamycin is a powerful inhibitor of the TOR (Target of Rapamycin) pathway, which is an evolutionarily conserved protein kinase, that plays a central role in plants and animals. Rapamycin is used globally as an immunosuppressant and as an anti-aging medicine. Despite widespread use, treatment efficiency varies considerably across patients, and little is known about potential side effects. Here we seek to investigate the effects of rapamycin by using Drosophila melanogaster as model system. Six isogenic D. melanogaster lines were assessed for their fecundity, male longevity and male heat stress tolerance with or without rapamycin treatment. The results showed increased longevity and heat stress tolerance for male flies treated with rapamycin. Conversely, the fecundity of rapamycin-exposed individuals was lower than for flies from the non-treated group, suggesting unwanted side effects of the drug in D. melanogaster. We found strong evidence for genotype-by-treatment interactions suggesting that a 'one size fits all' approach when it comes to treatment with rapamycin is not recommendable. The beneficial responses to rapamycin exposure for stress tolerance and longevity are in agreement with previous findings, however, the unexpected effects on reproduction are worrying and need further investigation and question common believes that rapamycin constitutes a harmless drug.

Recognizing obesity as a disease.

Obesity is a chronic, progressive, relapsing disease that impairs health and quality of life and shortens lifespan. Genetic and environmental factors contribute to its development and persistence. If left untreated, it worsens and leads to serious health consequences for those affected, as well as their offspring and future generations. Obesity complications drive many of the conditions that are seen routinely in clinical practice. By treating obesity first, many of these conditions improve or resolve. Given the seriousness of the disease, it is imperative that clinicians in primary and specialty care settings diagnose and treat or refer so that patients can receive appropriate treatment. Evidence-based treatment that is individualized and patient centered improves health and quality of life.

Catabolic activity of osteoblast lineage cells contributes to osteoclastic bone resorption in vitro.

Osteoblast lineage cells in human bone were recently shown to colonize eroded bone surfaces and to closely interact with osteoclasts. They proved to be identical to reversal cells and are believed to differentiate into bone-forming osteoblasts thereby coupling resorption and formation. However, they also exert catabolic activity that contributes to osteoclastic bone resorption, but this has not received much attention. Herein, we used co-cultures of primary human osteoblast lineage cells and human osteoclasts derived from peripheral blood monocytes to investigate whether a catabolic activity of osteoblast lineage cells could impact on osteoclastic bone resorption. Through a combination of immunofluorescence, in situ hybridization and time-lapse experiments, we show that MMP-13-expressing osteoblast lineage cells are attracted to and closely interact with bone-resorbing osteoclasts. This close interaction results in a strong and significant increase in the bone resorptive activity of osteoclasts - especially those making trenches. Importantly, we show that osteoclastic bone resorption becomes sensitive to inhibition of matrix metalloproteinases in the presence, but not in the absence, of osteoblast lineage cells. We propose that this may be due to the direct action of osteoblast-lineage-derived MMP-13 on bone resorption.

The glutamate transport inhibitor DL-Threo-ß-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. METHODS: Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability and glutathione content. Results were evaluated using one- and two-way ANOVA and Students two-tailed t-test, as relevant. RESULTS: In SN38-resistant HCT116 and LoVo cells, SLC1A1 expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at both mRNA and protein level, whereas SLC1A3 protein was undetectable. The changes in SLC1A1 expression were accompanied by parallel changes in DL-Threo-ß-Benzyloxyaspartic acid (TBOA)-sensitive, UCPH101-insensitive [(3)H]-D-Aspartate uptake, consistent with increased activity of SLC1A1 (or other family members), yet not of SLC1A3. DL-TBOA co-treatment concentration-dependently augmented loss of cell viability induced by SN38, while strongly counteracting that induced by oxaliplatin, in both HCT116 and LoVo cells. This reflected neither altered expression of the oxaliplatin transporter Cu(2+)-transporter-1 (CTR1), nor changes in cellular reduced glutathione (GSH), although HCT116 cell resistance per se correlated with increased cellular GSH. DL-TBOA did not significantly alter cellular levels of p21, cleaved PARP-1, or phospho-Retinoblastoma protein, yet altered SLC1A1 subcellular localization, and reduced chemotherapy-induced p53 induction. CONCLUSIONS: SLC1A1 expression and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point to novel treatment options in treatment-resistant CRC.