High-Fat Diet Affects Ceramide Content, Disturbs Mitochondrial Redox Balance, and Induces Apoptosis in the Submandibular Glands of Mice

Abstract

This is the first study to investigate the relationship between ceramides, the mitochondrial respiratory system, oxidative stress, inflammation, and apoptosis in the submandibular gland mitochondria of mice with insulin resistance (IR). The experiment was conducted on 20 male C57BL/6 mice divided into two equal groups: animals fed a high-fat diet (HFD; 60 kcal% fat) and animals fed a standard diet (10 kcal% fat). We have shown that feeding mice HFD induces systemic IR. We noticed that HFD feeding was accompanied by a significant increase in ceramide production (C18 1Cer, C18 Cer, C22 Cer, C24 1Cer, C24 Cer), higher activity of pro-oxidant enzymes (NADPH oxidase and xanthine oxidase), and weakened functioning of mitochondrial complexes in the submandibular glands of IR mice. In this group, we also observed a decrease in catalase and peroxidase activities, glutathione concentration, redox status, increased concentration of protein (advanced glycation end products, advanced oxidation protein products) and lipid (malondialdehyde, lipid hydroperoxide) peroxidation products, and enhanced production of tumor necrosis factor alpha (TNFα) and interleukin 2 (IL-2) as well as pro-apoptotic Bax in the submandibular gland mitochondria. In summary, HFD impairs salivary redox homeostasis and is responsible for enhanced oxidative damage and apoptosis in the submandibular gland mitochondria. The accumulation of some ceramides could boost free radical formation by affecting pro-oxidant enzymes and the mitochondrial respiratory chain.

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

“…This is not surprising because lipids, especially unsaturated ones, are relatively unstable compounds that are easily oxidized. Although lipid oxidation is a complex process, it occurs particularly when the antioxidant barrier is exhausted [26,40]. Thus, in our patients, changes in glutathione metabolism, reduced SOD activity as well as an increase in uric acid level may be crucial.…”

“…The concentration of plasma glutathione was assessed colorimetrically using the enzymatic reaction with NADPH, 5,5 -dithiobis-(2-nitrobenzoic acid) (DTNB), and GR [25,26]. The absorbance was measured at 412 nm.…”

“…Importantly, the redox status of obese cases was significantly reduced before the surgery, similarly to obese patients with MS at 3 and 6 months after the surgery. The redox status (ratio of reduced and oxidized glutathione) is used to assess the oxidative-reduction potential of the sample and characterizes the resultant ability of the biological system to counteract oxidative stress [26]. Thus, the oxidant/antioxidant balance is disturbed in patients before the bariatric treatment.…”

A Case-Control Study of Salivary Redox Homeostasis in Hypertensive Children. Can Salivary Uric Acid be a Marker of Hypertension?

“…Unfortunately, our study does not explain the causal relationship between oxidative stress and hyposalivation. However, it can be assumed that, as in other oxidative-stress-related diseases, products of protein and lipid oxidation can accumulate/aggregate in salivary glands, leading to secretory cell damage and a decrease in SWS secretion [21,22,49,68]. Indeed, oxidative stress is a key pathological factor responsible for hyposalivation in the course of many systemic diseases.…”

“…Similarly, the secretory function of salivary glands in hypertensive children has not been assessed so far. It is highly probable that, as in other oxidative stress-related diseases, the function of salivary glands as well as protein secretion in saliva are disturbed [21][22][23]. Because redox homeostasis cannot be characterized by a single biomarker, the aim of our study was to evaluate the salivary antioxidative barrier, the oxidative and nitrosative damage to proteins and lipids, as well as the secretory activity of salivary glands in children with hypertension compared to the controls.…”