Oral ionic liquid for the treatment of diet-induced obesity

Abstract

More than 70% of American adults are overweight or obese, a precondition leading to chronic diseases, including diabetes and hypertension. Among other factors, diets with high fat and carbohydrate content have been implicated in obesity. In this study, we hypothesize that the choline and geranate (CAGE) ionic liquid can reduce body weight by decreasing fat absorption through the intestine. In vitro studies performed using docosahexaenoic acid (DHA), a model fat molecule, show that CAGE forms particles 2 to 4 μm in diameter in the presence of fat molecules. Ex vivo permeation studies in rat intestine showed that formation of such large particles reduces intestinal fat absorption. In vivo, CAGE reduces DHA absorption by 60% to 70% compared with controls. DHA administered with CAGE was retained in the intestine even after 6 h. Rats fed with a high-fat diet (HFD) and 10 μL of daily oral CAGE exhibited 12% less body weight gain compared with rats fed with an HFD without CAGE for 30 d. Rats that were given CAGE also ate less food than the control groups. Serum biochemistry and histology results indicated that CAGE was well tolerated by the rats. Collectively, our data support the hypothesis that CAGE interacts with fat molecules to prevent their absorption through intestinal tissue and potentially providing a feeling of satiety. We conclude that CAGE offers an effective means to control body weight and a promising tool to tackle the obesity epidemic.

Mechanisms of action of ionic liquids on living cells: the state of the art

“… Marked changes in the gut microbiome have been observed in mice exposed to imidazolium-based ILs via drinking water; however, only mild hepatic and renal effects were observed (Young et al 2020 ). As a system biology potential application of ILs, it has been shown that in rats, oral delivery of a choline-based IL prevent the absorption of fat molecules through intestinal tissue, potentially providing a feeling of satiety (Nurunnabi et al 2019 ). Biochemistry and histology results indicated that the choline-based IL used in the study was tolerated by the rats.…”

“…As a system biology potential application of ILs, it has been shown that in rats, oral delivery of a choline-based IL prevent the absorption of fat molecules through intestinal tissue, potentially providing a feeling of satiety (Nurunnabi et al 2019 ). Biochemistry and histology results indicated that the choline-based IL used in the study was tolerated by the rats.…”

“…Whereas the discovery of the toxicity of ILs has broken the dreams of several researchers, it stimulated, on the other hand, a series of new studies interested in taking advantage of the affinity of ILs towards cells for applications in pharmacology, bio-medicine, and bio-nanotechnology (Hough et al 2007 ; Carson et al 2009 ; Stoimenovski et al 2012 ; Marrucho et al 2014 ; Williams et al 2014 ; Egorova et al 2017 ; Sahbaz et al 2017 ; Agatemor et al 2018 ; Benedetto and Ballone 2018a ; Tanner et al 2020 ; Shi et al 2020 ). For example, it has been shown that the oral delivery of a choline-based IL prevents the absorption of fat molecules through intestinal tissue in rats (Nurunnabi et al 2019 ). Apart from few very ad hoc “system biology” studies, as the one just mentioned, there are several studies highlighting the specificity of ILs towards cancer cells and their ability to kill those cells, leaving healthy cells almost unaffected (Kumar and Malhotra 2009 ; Malhotra and Kumar 2010 ; Wang et al 2015 ; Stromyer et al 2020 ).…”

Physical Properties of an Ionic Liquid Composed of Two Water-Soluble Vitamins and Enhanced Skin Permeation of Both Vitamins

“…ILs can extract specific active compounds from plants for pharmaceutical, nutritional, and cosmetic applications, such as the antimalarial drug artemisinin from the plant Artemisia annua [6]. Improvement of the gastrointestinal absorption of drugs by IL conversion [7][8][9] and improvement of the solubility of poorly soluble drugs using ILs [10,11] have been actively studied. Regarding enhancement of the percutaneous absorption of drugs examined in Pharmaceutics 2020, 12, 427 2 of 10 his study, it has been reported that skin permeation of drugs was enhanced by IL formation [12][13][14][15][16][17] and IL micelle formation as well [18,19].…”

Reply to Peiretti et al.: Effect of CAGE on fat uptake and food intake

“…We thank Peiretti et al (1) for their interest in our work (2) and for the suggestions for follow-up research. Peiretti et al (1) ask about the role of reduced food consumption in the observed effect on reduced weight gain.…”