Metabesity and urological cancers

Atan, Ali

doi:10.5152/tud.2017.66502

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…Collectively, DNP may be a treatment for an emerging global term called “metabesity” referring to all the co-morbidities associated with the over-nutritional phenotype such an increased incidence of insulin resistance, obesity, type 2 diabetes, sleep apnea, depression, inflammation, cardiovascular disease, hypertension, non-alcoholic fatty liver disease , but includes accelerated aging, neurodegeneration, and cancer. [2,184,185]. Studies are underway to explore an ever-expanding application of low dose mitochondrial uncoupling pharmacology.…”

Section: Concluding Thoughtsmentioning

confidence: 99%

2,4 Dinitrophenol as Medicine

Geisler¹

2019

Cells

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In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950’s to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and “morning sickness” anti-nausea medication targeting pregnant women in the 1950’s. The “thalidomide babies” became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients). Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of “social responsibility” allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines. The primary reason? It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction. It is known that mitochondrial uncouplers specifically target the entire organelle’s physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca2+) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca2+ overload. There is evidence that elevation of isoprostanes precedes disease onset, in Alzheimer’s Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS). Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair? If ROS production were managed, could disease onset due to aging be delayed or prevented? Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction? Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight neutral doses. DNP will be addressed as a treatment for “metabesity”, an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP’s induction of neurotrophic growth factors involved in neuronal heath, learning and cognition. For the first time in 80’s years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans. Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI).

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Section: Concluding Thoughtsmentioning

confidence: 99%

2,4 Dinitrophenol as Medicine

Geisler¹

2019

Cells

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“…With the increasing prevalence of MetS, the number of studies on MetS etiology and MetS -related diseases has also increased. Considering that MetS and its components should be evaluated in a broader spectrum, a concept termed metabesity has been introduced with the increasing recognition of their relationship with cancer [16]. In our study, it was concluded that the patients with MetS had a larger tumor size and a higher Fuhrman grade than those without MetS, but there was no difference between the two groups in terms of the pathological stage.…”

Section: Discussionmentioning

confidence: 62%

Impact of Metabolic Syndrome And Metabolic Syndrome Components on Tumor Aggresiveness of Renal Cell Carcinoma

Doğan

Atan

Ünsal

et al. 2021

Preprint

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Objective: The objective of this study was to evaluate the effects of Metabolic Syndrome (MetS) and MetS components on tumor size, Fuhrman grade and pathological T stage in renal cell carcinoma (RCC). Materials and Methods: The data of 151 patients who were operated for RCC between January 2010 and April 2018 were retrospectively reviewed according to the he National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and the effects of MetS and its components on tumor size, Fuhrman grade and pathological T stage were comparatively investigated. Results: Of the 151 patients operated for RCC in our clinic, 27.2% had MS, 29.1% had diabetes mellitus (DM), 41% had hypertension (HT), 68.3% had low high-density lipoprotein (HDL), 41% had elevated triglyceride (TGL) elevation, and 27.2% had obesity. It was found that the size of the tumor was statistically significantly increased in the presence of the metabolic criteria examined. There was a statistically significant increase in the Fuhrman grade of the patients with MetS, DM, low HDL, high TGL and obesity. In the presence of clinical conditions such as HT, low HDL and high TGL, there was a statistically significant increase in the pathological T stage. Conclusion: In patients undergoing surgery for RCC, MetS and its components had a statistically significant correlation with tumor size, Fuhrman grade, and pathological stage. If our results are supported by further studies, the correlation between MetS and RCC could be revealed more clearly.

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“…Recently, Dr. Alexander Fleming who is an endocrinologist added a different dimension to the definition of metabolic syndrome by introducing the concept of metabesity (2013). According to Dr. Fleming, metabesity describes all relevant conditions (diabetes mellitus, obesity, metabolic syndrome, cardiovascular disease, dyslipidaemia≥, cancer promoting factors and accelerated aging) which impose a serious burden on healthcare, and economic state [23].…”

Section: Introductionmentioning

confidence: 99%

Association between Metabolic Syndrome and Urolithiasis- Descriptive Study

Sj¹

2018

OAJUN

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The prevalence of kidney stones has been on the rise over the last 2 decades worldwide. Many studies have indicated a possible association between metabolic syndrome and kidney stone disease. Several hypotheses have been proposed to explain the pathophysiology of urolithiasis resulting from metabolic syndrome, amongst which are the insulin resistance and Randall's plaque hypothesis. Newer terminologies like Metabesity and Diabesity have been mentioned in recent literature. Many studies have found factors contributing to urolithiasis in patients suffering from metabolic syndrome, out of which obesity, overweight, and sedentary lifestyles have been identified as major etiological factors. This study is done to assess the association of urolithiasis and metabolic syndrome.

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Metabesity and urological cancers

Cited by 5 publications

References 39 publications

2,4 Dinitrophenol as Medicine

2,4 Dinitrophenol as Medicine

Impact of Metabolic Syndrome And Metabolic Syndrome Components on Tumor Aggresiveness of Renal Cell Carcinoma

Association between Metabolic Syndrome and Urolithiasis- Descriptive Study

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