4. Discussion
obesity, liver disease, obesity-related glomerulopathy, Fatty liver disease, overweight, mitochondrial dysfunction, weight loss, impairment of kidney function
OBESITY, OBESE, LIVER DISEASE, MITOCHONDRIAL DYSFUNCTION, PATHOGENESIS
We report that the daily consumption of a multi-ingredient supplement (MIS) designed to facilitate weight loss and mitochondrial function [Amongst an overweight population, there is a significantly lower mortality risk for individuals who are classified as overweight (BMI of 25.0–29.9 kg/mBy design, it is not possible to isolate which individual aspects of the seven-component MIS contributed to our observations; each has been shown to independently facilitate weight loss and/or improve mitochondrial function. We have previously reported that 5-, 7-, and 10-component MIS significantly reduced body weight and fat mass, and improved markers of in vivo metabolism in a murine model [The composition of MIS was designed to also include bioactive compounds that could facilitate mitochondrial function, given the established relationship between mitochondrial dysfunction and the pathogenesis of obesity. Increased consumption of food can lead to increased circulating lipids and carbohydrates, providing an ‘over-supply’ of energy substrates in metabolic tissues, which in turn stimulates the production of ROS [Fatty liver disease, when the triglyceride content of the liver organ weight surpasses 5%, is the most common liver disease associated with individuals who are obese [To examine the potential mechanisms of improved hepatic biomarkers, we performed additional molecular analysis. Growth differentiation factor-15 (GDF-15) is a novel cytokine member of the transforming growth factor β superfamily, whose expression increases in response to a variety of stimuli, including metabolic stress [Another potential mechanism via which the MIS may elicit metabolic and hepatic benefits is via circulating miRNAs contained within extracellular vesicles. EVs are emerging mechanisms of intercellular communication through the release or shedding of vesicles by various cells [Our examination of clinical hematology revealed a significant difference between the MIS and PLA treatment arms, with a significantly lower eosinophil count following 12 wks of MIS. Interestingly, eosinophil count has been previously shown to be positively correlated with BMI up to a plateau of 40 kg/mAn impairment of kidney function, specifically obesity-related glomerulopathy [We acknowledge several limitations of the current study. A possible limitation of this study is that we did not have full control of physical activity and/or dietary intake during the experimental period. At the onset of the study, we provided simple diet information (the Canadian Food Guide) and only provided diet and activity guidelines at the inception to determine the potential effect of an MIS in a free-living scenario without intensive behavioral intervention. The lack of strict dietary and/or exercise controls and the impact of COVID-19 in the third inception cohort were also factors that may have contributed to the increase in body weight in the control group and may represent a potential attenuation of weight loss in the MIS group. Finally, the current study was conducted for 12 wks and thus we could not observe the sustainability of the effects over a longer period. Future studies should address interventions with longer durations.