75-OR: Dietary Nitrate and Fecal Transplantation Prevent Cardiac Dysfunction and Attenuate Left Ventricular Mitochondrial Reactive Oxygen Species Emission in High-Fat Diet-Fed Mice

Bradykinin signaling has been proposed to play either protective or deleterious roles in the development of cardiac dysfunction in response to various pathological stimuli. To further define the role of bradykinin signaling in the diabetic heart, we examined cardiac function in mice with genetic ablation of both bradykinin B1 and B2 receptors (B1RB2R−/−) in the context of the Akita model of insulin-deficient type 1 diabetes (Ins2Akita/+). In 5-month-old diabetic and nondiabetic, wild-type and B1RB2R−/− mice, in vivo cardiac contractile function was determined by left-ventricular (LV) catheterization and echocardiography. Reactive oxygen species levels were measured by 2′-7′-dichlorofluorescein diacetate fluorescence. Mitochondrial function and ATP synthesis were determined in saponin-permeabilized cardiac fibers. LV systolic pressure and the peak rate of LV pressure rise and decline were decreased with diabetes but did not deteriorate further with loss of bradykinin signaling. Wall thinning and reduced ejection fractions in Akita mouse hearts were partially attenuated by B1RB2R deficiency, although other parameters of LV function were unaffected. Loss of bradykinin signaling did not increase fibrosis in Ins2Akita/+ diabetic mouse hearts. Mitochondrial dysfunction was not exacerbated by B1RB2R deficiency, nor was there any additional increase in tissue levels of reactive oxygen species. Thus, loss of bradykinin B2 receptor signaling does not abrogate the previously reported beneficial effect of inhibition of B1 receptor signaling. In conclusion, complete loss of bradykinin expression does not worsen cardiac function or increase myocardial fibrosis in diabetes.

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Long-term, high-fat feeding exacerbates short-term increases in adipose mitochondrial reactive oxygen species, without impairing mitochondrial respiration

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00028.2020 ◽

2020 ◽

Vol 319 (2) ◽

pp. E376-E387 ◽

Cited By ~ 2

Author(s):

Valerie Politis-Barber ◽

Henver S. Brunetta ◽

Sabina Paglialunga ◽

Heather L. Petrick ◽

Graham P. Holloway

Keyword(s):

Reactive Oxygen Species ◽

Mitochondrial Respiration ◽

Reactive Oxygen ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

High Fat ◽

Respiratory Capacity ◽

Tissue Weight ◽

Mitochondrial Respiratory

White adipose tissue (WAT) dysfunction in obesity is implicated in the onset of whole body insulin resistance. Alterations in mitochondrial bioenergetics, namely impaired mitochondrial respiration and increased mitochondrial reactive oxygen species (mtROS) production, have been suggested to contribute to this metabolic dysregulation. However, techniques investigating mitochondrial function are classically normalized to tissue weight, which may be confounding when considering obesity-related adipocyte hypertrophy. Furthermore, the effect of long-term high-fat diet (HFD) on mtROS in WAT has yet to be elucidated. Therefore, we sought to determine the HFD-mediated temporal changes in mitochondrial respiration and mtROS emission in WAT. C57BL/6N mice received low-fat diet or HFD for 1 or 8 wk and changes in inguinal WAT (iWAT) and epididymal WAT (eWAT) were assessed. While tissue weight-normalized mitochondrial respiration was reduced in iWAT following 8-wk HFD-feeding, this effect was mitigated when adipocyte cell size and/or number were considered. These data suggest HFD does not impair mitochondrial respiratory capacity per adipocyte within WAT. In support of this assertion, within eWAT compensatory increases in lipid-supported and maximal succinate-supported respiration occurred at 8 wk despite cell hypertrophy and increases in WAT inflammation. Although these data suggest impairments in mitochondrial respiration do not contribute to HFD-mediated WAT phenotype, lipid-supported mtROS emission increased following 1-wk HFD in eWAT, while both lipid and carbohydrate-supported mtROS were increased at 8 wk in both depots. Combined, these data establish that while HFD does not impair adipocyte mitochondrial respiratory capacity, increased mtROS is an enduring physiological occurrence within WAT in HFD-induced obesity.

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Single bulb garlic oil improves interleukin-6 via decreased reactive oxygen species (ROS) in high-fat diet male mice

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2019.v38.100-107 ◽

2019 ◽

Vol 38 (2) ◽

pp. 100 ◽

Cited By ~ 1

Author(s):

Riza Rahayu Ilmawati ◽

Abdul Gofur ◽

Sri Rahayu Lestari

Keyword(s):

Reactive Oxygen Species ◽

Interleukin 6 ◽

High Fat Diet ◽

Antioxidant Properties ◽

Reactive Oxygen ◽

Optimum Dose ◽

Oxygen Species ◽

Male Mice ◽

High Fat ◽

Garlic Oil

Background High-fat diet (HFD) is highly responsible for the development of excessive reactive oxygen species (ROS). ROS and low-density lipoprotein (LDL) then trigger macrophage activation to secrete interleukin-6 (IL-6). Single bulb garlic or in Indonesian called bawang lanang is traditional medicine that possesses strong antioxidant properties. This study aimed to evaluate the effect of single bulb garlic oil (SBGO) on ROS, IL-6, and lymphocyte density in HFD-fed male mice. Methods This was an experimental study on 24 male mice randomly subdivided into 6 groups: one group was fed a normal diet, whereas the remaining five groups were fed HFD for 45 days and were then treated with single bulb garlic oil 0 mg/kg, simvastatin 26 mg/kg BW, single bulb garlic oil 12.5 mg/kg BW, 25 mg/kg BW, and 50 mg/kg BW respectively for the next 35 days. At the end of treatment, the mice were dissected for collection of (i) serum in order to measure ROS and IL-6 levels using ELISA, (ii) aortas to measure IL-6 expression using immunohistochemistry-fluorescence (IHC-F) and to obtain lymphocytes from bone marrow and spleen which were then counted using a light microscope. Results Our results indicated that SBGO decreased the ROS level, IL-6 level, IL-6 expression, and lymphocyte density in HFD mice. SBGO 12.5 mg/kg BW is the optimum dose in our study to reduce inflammation in HFD male mice. Conclusion SBGO is useful to reduce inflammation and improve antioxidant imbalance, thus might be a potential antiatherogenic agent.

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