Use of Dinitrophenol in Obesity and Related Conditions

Abstract

tainly do not show hyperplasia in the sense in which gynecologic pathologists use the term. But there is no doubt, on the basis of considerable experimental evidence, that such a condition can be reproduced. I believe that the authors' results would be more clearly denned if they did not interrupt their study so frequently by the disturbing factor of curettage. Such studies as these add additional evidence in support of the broad prin¬ ciple that functional uterine bleeding, including that of normal menstruation, is due to a withdrawal or abrupt diminution in the level of the folliculin content of the blood. If a maturing follicle or a maturing corpus luteum is excised, bleeding results after an interval of varying length. If a castrated animal is given theelin daily for seven or eight days, bleeding results, but not until some days after the withdrawal of the theelin.I have elsewhere summarized the evidence for this rather fundamental principle in the causation of uterine bleeding and have discussed also the equally important rôle played by the reciprocal effects of the ovary and the anterior hypophysis. The authors mentioned that in some cases evidences of hypersecretion were seen in the endometrium after the injection of theelin. This is contrary to accepted ideas, if they mean a real secretory activity of the epithelium such as is found in the pregravid or secretory phase of the cycle. Indeed, one of the criteria in the microscopic diagnosis of hyperplasia of the endometrium is the absence of any secretory activity.Dr. J. P. Pratt, Detroit : Dr. Werner and Dr. Collier have opened the possibility of many problems for discussion. Among the most important of these is the demonstration of concrete anatomic and physiologic evidence of reaction to theelin by the human ovary. This contribution is especially welcome in view of the fact that animal experimentation with hormones has advanced far beyond the clinical application and that results of animal reactions have been applied by analogy to clinical problems with frequent unsatisfactory consequences. Among animals, many striking variations appear in their reaction to hormones, even in closely related species. This demonstration of reaction in the human subject, therefore, is extremely valu¬ able. Separation of their objective from their subjective evi¬ dence is most important, for the latter is difficult to evaluate. For this reason, observation of a change in such symptoms as libido may be open to question. How much of the change was due to psychotherapy? Reports of attempts to substitute for ovarian deficiency are numerous, but the authors hold a unique position in reporting unquestionable evidence of reaction to ovarian hormone in a series of cases in which the ovaries were absent. Even in their series considerable individual variation in response to a given dosage was noted. This emphasizes the difficulty of estimating the amount of hormone needed to sub¬ stitute for deficiency when the ovaries are present but are not functioning normally. There is no satisfact...

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

“…Since then, it has also been used as a dye, wood preserver, herbicide and photographic developer. It was Maurice Tainter at Stanford University in 1933 who discovered that the human consumption of DNP led to significant weight loss and soon it was popularised as a weight loss drug [8]. It was included in over-the-counter medications and was sold to the public without requiring a prescription.…”

“…Its use for those wishing to lose weight was encouraged by reports of rapid, safe weight loss [7,8]. DNP can cause a significant increase in the basal metabolic rate [7,8].…”

“…DNP can cause a significant increase in the basal metabolic rate [7,8]. This leads to weight loss by burning more fat and carbohydrates [9], and weight loss of up to 1.5 kg per week is reported without significant side effects.…”

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

“…However, CZ5 had no remarkable effects on body weight and adiposity in SD mice, as the enhanced EI was able to compensate for the increased EE. These therapeutic effects induced by CZ5 appear to mimic those produced by overexpression of UCPs in SKM and WAT [12][13][14], which are in contrast to those effects reported for obesity treatment with non-specific uncouplers in humans or rodents [16,17].…”

“…Yet it remains to be verified how these UCPs are regulated by physiological ligands [15]. Pharmacological evidence for the effectiveness of uncoupling includes the potent anti-obesity effect observed with 2,4-dinitrophenol (DNP), a chemical uncoupler with a non-specific effect widely used in the 1930s [16]. However, severe side effects, such as uncontrolled hyperthermia at toxic doses, prevented the further development of other anti-obesity uncoupling agents largely due to their narrow therapeutic window [17].…”