Current Updates in the Medical Management of Obesity

Khan, Abdullah; Raza, Shahzad; Khan, Yusra Habib; Aksoy, Tulay; Khan, Monis; Weinberger, Yitzchak; Goldman, Joel M.

doi:10.2174/187221412800604644

Cited by 23 publications

(17 citation statements)

References 74 publications

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“…To automatically control diet-induced obesity in a self-sufficient manner, we functionally coupled the LSR sensor device to expression of the clinically licensed anorectic peptide hormone pramlintide7, which suppresses appetite, promotes satiety5 and slows gastric emptying44, thereby limiting high-caloric food intake, attenuating hyperlipidemic blood levels, reducing body weight and restoring the energy homeostasis of the organism. Therefore, we replaced SEAP of pMG10 by pramlintide and validated the resulting vector pK146 (P TtgR1 -Pram-pA) for LSR-controlled pramlintide production using enzyme-linked immunosoebent assay (ELISA; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In brief, 50 μl of heat-inactivated serum (30 min, 65 °C), centrifuged for 30 s at 14,000 g , were transferred to a well of a 96-well plate containing 50 μl inactivation buffer and incubated for 10 min at 22 °C. Next, 50 μl of freshly prepared substrate reagent (50 μl CSPD [3-(4-methoxyspiro[1,2-dioxetane-3,2′(5′-chloro)-tricyclo(3.3.1.137 decane]-4-yl)phenyl phosphate] mixed with 950 μl substrate buffer) was added to each well and incubated for 10 min at 22 °C before light emission was recored at 477 nm using the Envision 2104 multilabel plate reader (Perkin Elmer).…”

Section: Methodsmentioning

confidence: 99%

“…Obesity is at the origin of a wide range of diseases such as cardiovascular disorders, type 2 diabetes, obstructive sleep apnea, osteoarthritis, asthma and certain types of cancer, and has become a leading preventable cause of death with dramatically increasing prevalence, affecting up to 1.5 billion people in industrialized and developing countries234. A sustainable change in lifestyle, including dieting and physical exercise, is the pillar for the treatment of obesity that can be complemented by gastric balloon and bariatric surgery to assist weight loss4 and by taking anti-obesity drugs to reduce appetite or fat absorption567. However, dieting often shows limited success8, surgery is associated with significant risks9 and only some anti-obesity drugs with modest efficacy10 remain on the market after many have been withdrawn because of side effects11121314, and few have entered clinical trials since15.…”

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confidence: 99%

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A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

2013

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Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

2013

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“…Obesity, and its correlated metabolic and physiological problems including type 2 diabetes, cardiovascular disease and osteoarthritis, is one of the leading causes of a severely reduced quality of life and a shortened lifespan [1].…”

Section: Introductionmentioning

confidence: 99%

Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

2014

J Endocrinol Metab

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Background: AOD9604 is the C-terminal fragment of human growth hormone (hGH). Early stage studies with AOD9604 have shown positive activities on fat metabolism. As a result the use of AOD9604 to improve metabolic profiles may be plausible. For these uses, the safety of AOD9604 needs to be clearly demonstrated. Here we report the findings from studies involving the genotoxicological, toxicological and pharmacokinetic testing of AOD9604.

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“…Obesity has a complicated, often multifactorial etiology that often makes its effective management difficult 6,7. A multifaceted approach that often requires lifestyle modification, dietary alterations, changes in physical activity patterns, as well as pharmacotherapy and/or surgery is often required to achieve sustained weight management in patients with obesity 6,7.…”

Section: Introductionmentioning

confidence: 99%

Phentermine and topiramate for the management of obesity: a review

Cosentino¹,

Conrad²,

Uwaifo³

2013

DDDT

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Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.

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Current Updates in the Medical Management of Obesity

Cited by 23 publications

References 74 publications

A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

Phentermine and topiramate for the management of obesity: a review

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