Effects of Chronic Electronic Vapor Exposure on Body Weight, Appetite, and Metabolism

Cigarette smokers weigh less than non-smokers and gain weight upon smoking cessation. Electronic cigarettes (E-cigs) have been used as a smoking cessation tool among many, however, their effects on metabolism, appetite, and energy balance are virtually unknown. This study compares the effects of chronic E-cig vapor exposure on body mass, food intake, metabolism, and body composition in mice. We hypothesized that E-cig exposure would elicit similar changes on body mass, body composition, food intake, and metabolic and appetite-regulating markers as conventional cigarettes (i.e. 3R4F reference cigarette). Female C57BL/6 mice were exposed to filtered room air (n=15), mainstream smoke from 3R4F reference cigarettes (n=15), or E-cig vapor (n=15) for a total of 8-months (4 h/d, 5d/wk). Body mass, food intake, metabolic and appetite-regulating markers, heat production, and body composition were measured. Weight gain, fat-free mass (FFM), and fat mass were significantly elevated in E-cig and control mice compared to 3R4F mice. Food consumption and heat production (kcal expended/hr) was significantly increased in E-cig mice compared to control and 3R4F mice. Appetite-regulating markers (NPY, POMC, leptin, and GLP-1) were similar between all groups. Mitochondrial uncouplers (UCP-1 and UCP-3) remained unchanged between E-cig and control groups, however, UCP-1 was significantly elevated in E-cig mice compared to 3R4F mice and UCP-3 was significantly elevated in control vs. 3R4F mice. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were also significantly elevated in E-cig and 3R4F mice compared to control mice, while respiratory exchange ratios (RER) were unchanged. Unlike conventional cigarettes, we found that E-cig exposure did not elicit reductions in total body or adipose mass. This suggests the effects of E-cig may not be the same as that occurring with traditional tobacco cigarettes, or that the exposure to nicotine and/or other chemicals in the E-cig liquid elicits a different response on appetite or feeding behavior. While E-cig mice increased food intake, their basal metabolism was also elevated, suggesting energy dissipation resulting in a similar net energy balance compared to control mice. Further studies are needed to evaluate the effect that flavorings and/or the compounds produced in E-cig vapor exert on metabolism, energy balance, and the neural regulation of appetite

The intracellular chloride ion channel protein CLIC1 undergoes a redox-controlled structural transition.

Most proteins adopt a well defined three-dimensional structure; however, it is increasingly recognized that some proteins can exist with at least two stable conformations. Recently, a class of intracellular chloride ion channel proteins (CLICs) has been shown to exist in both soluble and integral membrane forms. The structure of the soluble form of CLIC1 is typical of a soluble glutathione S-transferase superfamily protein but contains a glutaredoxin-like active site. In this study we show that on oxidation CLIC1 undergoes a reversible transition from a monomeric to a non-covalent dimeric state due to the formation of an intramolecular disulfide bond (Cys-24-Cys-59). We have determined the crystal structure of this oxidized state and show that a major structural transition has occurred, exposing a large hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 dimer maintains its ability to form chloride ion channels in artificial bilayers and vesicles, whereas a reducing environment prevents the formation of ion channels by CLIC1. Mutational studies show that both Cys-24 and Cys-59 are required for channel activity

Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution.

Abstract CLIC1 (NCC27) is a member of the highly conserved class of chloride ion channels that exists in both soluble and integral membrane forms. Purified CLIC1 can integrate into synthetic lipid bilayers forming a chloride channel with similar properties to those observed in vivo. The structure of the soluble form of CLIC1 has been determined at 1.4-A resolution. The protein is monomeric and structurally homologous to the glutathioneS-transferase superfamily, and it has a redox-active site resembling glutaredoxin. The structure of the complex of CLIC1 with glutathione shows that glutathione occupies the redox-active site, which is adjacent to an open, elongated slot lined by basic residues. Integration of CLIC1 into the membrane is likely to require a major structural rearrangement, probably of the N-domain (residues 1–90), with the putative transmembrane helix arising from residues in the vicinity of the redox-active site. The structure indicates that CLIC1 is likely to be controlled by redox-dependent processes

The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

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Effect of Morning and Evening Exercise on Energy Balance: A Pilot Study

The purpose of this study was to evaluate the feasibility and acceptability of randomizing adults with overweight and obesity (BMI 25–40 kg/m2) to morning (06:00–10:00) or evening (15:00–19:00) aerobic exercise. Participants completed four exercise sessions per week in the morning (AM, n = 18) or evening (PM, n = 15). The exercise program was 15 weeks and progressed from 70 to 80% heart rate maximum and 750–2000 kcal/week. Bodyweight, body composition, total daily energy expenditure (TDEE), energy intake (EI), sleep, sedentary behavior (SB), non-exercise physical activity (NEPA), and maximal aerobic capacity were assessed at baseline and week 15. Study retention was 94% and adherence to the supervised exercise program was ≥90% in both groups. Weight change was −0.9 ± 2.8 kg and −1.4 ± 2.3 kg in AM and PM, respectively. AM and PM increased TDEE (AM: 222 ± 399 kcal/day, PM: 90 ± 150 kcal/day). EI increased in AM (99 ± 198 kcal/day) and decreased in PM (−21 ± 156 kcal/day) across the intervention. It is feasible to randomize adults with overweight and obesity to morning or evening aerobic exercise with high levels of adherence. Future trials are needed to understand how the timing of exercise affects energy balance and body weight regulation