Abstract Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin ...resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.
Body mass index of 30 kg/m2 or higher is used to identify individuals with obesity. In the last 3 decades, the worldwide prevalence of obesity has increased 27.5% for adults and 47.1% for children. ...Obesity is the result of complex relationships between genetic, socioeconomic, and cultural influences. Consumption patterns, urban development, and lifestyle habits influence the prevalence of obesity. The condition may be the result of disease or pharmacologic treatment. It may also be a risk factor for the development of comorbid conditions. Persons who are obese have less school attendance, reduced earning potential, and higher healthcare costs that may result in an economic burden on society. A review of the prevalence and economic consequences of obesity is provided. Potential causes and comorbidities associated with obesity are also discussed.
Updates on obesity pharmacotherapy Velazquez, Amanda; Apovian, Caroline M.
Annals of the New York Academy of Sciences,
January 2018, 2018-01-00, 20180101, Letnik:
1411, Številka:
1
Journal Article
Recenzirano
Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, ...including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short‐term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long‐term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA‐approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity‐centric prescribing for mental illness, neurological disorders, and contraceptive planning.
Objective:
To formulate clinical practice guidelines for the pharmacological management of obesity.
Participants:
An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical ...writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society.
Evidence:
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.
Consensus Process:
One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence.
Conclusions:
Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.
Purpose of Review
Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle ...therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity. This development is preceded by increased understanding of the underpinnings of energy regulation and neurohormonal pathways involved in energy homeostasis.
Recent Findings
Though there are approved anti-obesity drugs available in the USA, newer drugs are now in the pipeline for development given the urgent need. This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist velneperit, zonisamide-bupropion Empatic, cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 GLP-1 analogues semaglutide and oral equivalents, amylin mimetics davalintide, dual amylin and calcitonin receptor agonists, dual action GLP-1/glucagon receptor agonists oxyntomodulin, triple agonists tri-agonist 1706, peptide YY, leptin analogues combination pramlintide-metreleptin), and other novel targets (methionine aminopeptidase 2 inhibitor beloranib, lipase inhibitor cetilistat, triple monoamine reuptake inhibitor tesofensine, fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36).
Summary
With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.
Objective:
To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.
Design and Methods:
CONTRAVE Obesity ...Research‐II (COR‐II) was a double‐blind, placebo‐controlled study of 1,496 obese (BMI 30‐45 kg/m2) or overweight (27‐45 kg/m2 with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co‐primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.
Results:
Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (−6.5% vs. −1.9%) and week 56 (−6.4% vs. −1.2%). More NB32‐treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant‐reported weight‐related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.
Conclusion:
NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.
Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis. Modest weight-loss (≥ 5% but < 10%) can minimize and reduce diabetes-associated ...complications, and significant weight-loss can potentially resolve disease. Treatment guidelines recommend that intensive lifestyle interventions, pharmacologic therapy, and/or metabolic surgery be considered as options for patients with T2D and obesity. The benefits and risks of such interventions should be evaluated in the context of their weight-loss potential, ability to sustain weight change, side effect profile, and costs. Antihyperglycemia therapies have considerable effects on patient weight, prompting careful consideration of weight-loss or weight-neutral therapies for patients with T2D who also have obesity. Metformin, sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), α-glucosidase inhibitors, and amylin mimetics promote weight-loss. Dipeptidyl peptidase-4 inhibitors and fixed-ratio insulin/GLP-1 RA combination therapies (IDegLira, iGlarLixi) appear to be weight-neutral. Thiazolidinediones, insulin secretagogues (sulfonylureas, meglitinides), and insulins are associated with weight gain. Sulfonylureas are additionally associated with a higher risk of serious hypoglycemia from hyperinsulinemia, making them less suitable for the treatment of patients who are overweight or have obesity. Patients are often overtitrated on basal insulin, resulting in an increased risk of hypoglycemia and weight gain without achieving glycemic goals. Given these observations, the effects of antihyperglycemia agents on weight should be considered when individualizing T2D therapy.
Funding
: Sanofi US, Inc.
Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and ...bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.
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•CD4+ T cells from healthy older people preferentially produce a Th17 profile•Autophagy, but not mitophagy, knockdown activates a Th17 profile in “young” cells•Mitochondrial ROS is needed, but not sufficient, for a Th17 profile in “young” cells•Metformin improves autophagy and mitochondria in parallel to decrease inflammaging
We uncovered a dominant Th17 inflammaging profile made by CD4+ T cells. Knockdown of autophagy in T cells from young subjects activates this profile. In vitro metformin improves autophagy and mitochondrial function in parallel to ameliorate Th17 inflammaging. Oral metformin intervention improves T cell autophagy in people, indicating potential use for age-associated inflammation.
Obesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss ...current epidemiological data on the prevalence of obesity in European countries.
We identified relevant published studies by means of a MEDLINE search (1990-2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each country's overall population.
In Europe, the prevalence of obesity (body mass index > or = 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe.
In Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.
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