Abstract
Cardiometabolic complications such as the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) are major causes of global morbidity and mortality. As sugar-sweetened beverages (SSBs) are implicated in this process, this study aimed to obtain greater mechanistic insights. Male Wistar rats (~200 g) were gavaged with a local SSB every day for a period of six months while the control group was gavaged with an iso-volumetric amount of water. Experimental dosages were calculated according to the surface area-to-volume ratio and were equivalent to 125 mL/day (in human terms). A proteomic analysis was performed on isolated liver samples and thereafter, markers of endoplasmic reticulum (ER) stress, antioxidant/oxidant capacity, calcium regulation, and mitochondrial functionality were assessed. These data show that SSB consumption resulted in (a) the induction of mild hepatic ER stress; (b) altered hepatic mitochondrial dynamics; and (c) perturbed calcium handling across mitochondria-associated ER membranes. Despite significant changes in markers of ER stress, the antioxidant response and calcium handling (proteomics data), the liver is able to initiate adaptive responses to counteract such stressors. However, the mitochondrial data showed increased fission and decreased fusion that may put the organism at risk for developing insulin resistance and T2DM in the longer term.
Highlights
Cardiometabolic complications such as metabolic syndrome and Type 2 Diabetes Mellitus (T2DM)pose major global burdens of morbidity and result in ~19 million deaths annually [1]
As the underlying mechanisms driving sugar-sweetened beverages (SSBs)-mediated cardiometabolic complications remain poorly understood, we employed a unique in-house developed in-vivo rat model of SSB intake to assess the effects of 6-months consumption on the liver
The main findings from moderate but frequent SSB intake are as follows: (a) the induction of mild hepatic endoplasmic reticulum (ER) stress; (b) altered hepatic mitochondrial dynamics and c) perturbed calcium handling across mitochondria-associated ER membranes (MAMs)
Summary
Pose major global burdens of morbidity and result in ~19 million deaths annually [1]. Their prevalence rapidly increased over the past few decades and they continue to rise, especially in low- and middle-income countries. As SSBs contain excessive amounts of rapidly absorbable carbohydrates such as glucose and high-fructose corn syrup [8], the glycemic load on the liver sharply increases following its consumption. Regular SSB consumption and an increased metabolic load can lead to hepatocyte dysfunction that can present in the form of endoplasmic reticulum (ER) stress, which, in turn, is strongly implicated in T2DM onset [9,10,11]
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