Hydrogen Sulfide Prevents Mesenteric Adipose Tissue Damage, Endothelial Dysfunction, and Redox Imbalance From High Fructose Diet-Induced Injury in Aged Rats

Abstract

A high fructose diet (HFD) and advanced age are key factors for the gradual loss of physiological integrity of adipose tissue. Endogenous hydrogen sulfide (H2S) has beneficial effects on cytoprotection and redox balance. But its interactive effects on age-related damage of mesenteric vessels and connective and adipose tissues (MA) during HFD which could be the base of the development of effective physiological-based therapeutic strategy are unknown. The aim of study was to investigate age- and HFD-induced mesenteric cellular changes and activities of enzymes in H2S synthesis and to test the effects of sodium hydrosulfide (NaHS) which is considered an H2S donor on them. Adult and aged male rats on a standard diet (SD) or 4-week HFD were exposed to acute water-immersion restraint stress (WIRS) for evaluation of mesenteric subcellular and cellular adaptive responses by electron microscopy. The effects of exogenous NaHS (5.6 mg/kg/day for 9 days) versus vehicle on mesentery changes were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), thiosulfate-dithiol sulfurtransferase (TST), and sulfite oxidase (SO) were examined by spectrophotometry. In both adult and aged SD groups, treatment with NaHS protected mesenteric cells after WIRS. In both groups, the treatment with NaHS also protected MA mitochondria, microvascular endothelial and sub-endothelial structures, and fibroblasts versus the vehicle-treated group that had signs of damage. HFD increased MA injury and mitochondrial changes in both aged and adult rats. HFD-associated malfunction is characterized by low activities of CSE, CBS, TST, SO, and increased TBARS. Finally, we demonstrated that pretreatment with NaHS inhibited MA and mitochondria alterations in aged rats exposed to HFD and WIRS, lowered TBARS, and enhanced H2S enzyme activities in contrast to the vehicle-treated group. Mitochondrial integrity alterations, endothelial damage, and redox imbalance are key factors for rat mesenteric adipose tissue damage during advanced age. These alterations and MA hypertrophic changes retain the central for HFD-induced damage. Moreover, H2S signaling contributes to MA and mitochondria redox balance that is crucial for advanced age and HFD injury. The future study of H2S donors’ effects on mesenteric cells is fundamental to define novel therapeutic strategies against metabolic changes.

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

“…stress, intensive physical load, or nutritional deprivation (Morigny et al 2016 ). Our data of ultracellular changes of mesenteric white adipocytes during experimental obesogenic diet and stress has shown defragmentation of the intracellular big fat drop to smaller droplets of fat into the cytoplasm of white adipocytes or outside of the cell, lipid-laden phagolysosomes and detective ring-like mitochondria (Revenko et al 2021 ). Thus, Selye’s pioneered observational study was a great step in understanding the homeostatic role of BAT in systemic energy balance and survival/adaptative mechanisms in the whole organism.…”

“…It could be the valid risk factor for the onset of metaflammation, the tissue-specific alterations based on chronic low-grade inflammation linked with abnormal metabolism related to cellular damage and oxidative stress, as well as accelerated cellular senescence and oncogenes activation (Tchkonia et al 2010 ). Our animal model data about mesenteric adipose tissue has shown a role of visceral lipotoxicity in age-related endothelial dysfunction, redox disbalance, and the positive effect of hydrogen sulfide influence on decreased metaflammation (Revenko et al 2018 , 2021 ). It could be a potential therapeutic approach for obesity-related several serious illnesses, especially mesenteric chronic inflammation of the gastrointestinal tract, cardiovascular diseases, diabetes mellites 2 type (T2D) related disorders, infertility, and cancer.…”

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

“…It’s very similar to WAT response during metabolic demand, e.g., stress, intensive physical load, or nutritional deprivation (Morigny et al 2016 ). Our data of ultracellular changes of mesenteric white adipocytes during experimental obesogenic diet and stress have shown defragmentation of the intracellular big fat drop to smaller droplets of fat into the cytoplasm of white adipocytes or outside of the cell, lipid-laden phagolysosomes and detective ring-like mitochondria (Revenko et al 2021 ). Thus, Selye’s pioneered observational study was a great step in understanding the homeostatic role of BAT in systemic energy balance and survival/adaptative mechanisms in the whole organism.…”

“…It could be the valid risk factor for the onset of metaflammation, the tissuespecific alterations based on chronic low-grade inflammation linked with abnormal metabolism related to cellular damage and oxidative stress, as well as accelerated cellular senescence and oncogenes activation (Tchkonia et al 2010). Our animal model data about mesenteric adipose tissue have shown a role of visceral lipotoxicity in agerelated endothelial dysfunction, redox disbalance, and the positive effect of hydrogen sulfide influence on decreased metaflammation (Revenko et al 2018(Revenko et al -2021. It could be a potential therapeutic approach for obesity-related several serious illnesses, especially mesenteric chronic inflammation of the gastrointestinal tract, cardiovascular diseases, diabetes mellitus 2 type (T2D) related disorders, infertility, and cancer.…”

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors

“…To avoid bias, the rats were placed in a random manner into four groups: Group 1: negative control group ( n = 6), in which the rats received saline (Sal. group); Group 2: DEX group ( n = 6), in which the rats received a subcutaneous injection of with Dexamethasone (DEX) (Amriya, for pharmaceutical industries, Egypt) (0.6 mg/Kg/day) for six days per week for two weeks [ 18 ]; Group 3: DEX + NaHS group ( n = 6), in which the rats received DEX as mentioned in Group 2, in addition to an intraperitoneal injection of NaHS (the donor of H2S) (Acros organics © Belgium), dissolved in saline (5 mg/Kg/day) for two weeks [ 19 ]; and Group 4: DEX + AOAA ( n = 6), in which the rats received DEX as mentioned in Group 2. In addition, they received intraperitoneal injection of Aminooxyacetic acid (AOAA), a blocker of H2S (Acros organics © Belgium) (10 mg/Kg/day) for two weeks.…”