دورية أكاديمية
Independent of mitochondrial respiratory function, dietary nitrate attenuates HFD-induced lipid accumulation and mitochondrial ROS emission within the liver.
| العنوان: | Independent of mitochondrial respiratory function, dietary nitrate attenuates HFD-induced lipid accumulation and mitochondrial ROS emission within the liver. |
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| المؤلفون: | DesOrmeaux GJ; Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada., Petrick HL; Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada., Brunetta HS; Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.; Department of Physiological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil., Holloway GP; Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. |
| المصدر: | American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2021 Aug 01; Vol. 321 (2), pp. E217-E228. Date of Electronic Publication: 2021 Jul 06. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD. : American Physiological Society |
| مواضيع طبية MeSH: | Diet, High-Fat* , Lipid Metabolism*, Liver/*metabolism , Mitochondria/*metabolism , Nitrates/*metabolism , Reactive Oxygen Species/*metabolism, AMP-Activated Protein Kinases/metabolism ; Animals ; Homeostasis ; Insulin/metabolism ; Male ; Mice, Inbred C57BL ; Mice |
| مستخلص: | The liver is particularly susceptible to the detrimental effects of a high-fat diet (HFD), rapidly developing lipid accumulation and impaired cellular homeostasis. Recently, dietary nitrate has been shown to attenuate HFD-induced whole body glucose intolerance and liver steatosis, however, the underlying mechanism(s) remain poorly defined. In the current study, we investigated the ability of dietary nitrate to minimize possible impairments in liver mitochondrial bioenergetics following 8 wk of HFD (60% fat) in male C57BL/6J mice. Consumption of a HFD caused whole body glucose intolerance ( P < 0.0001), and within the liver, increased lipid accumulation ( P < 0.0001), mitochondrial-specific reactive oxygen species emission ( P = 0.007), and markers of oxidative stress. Remarkably, dietary nitrate attenuated almost all of these pathological responses. Despite the reduction in lipid accumulation and redox stress (reduced TBARS and nitrotyrosine), nitrate did not improve insulin signaling within the liver or whole body pyruvate tolerance ( P = 0.313 HFD vs. HFD + nitrate). Moreover, the beneficial effects of nitrate were independent of changes in weight gain, 5' AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) signaling, mitochondrial content, mitochondrial respiratory capacity and ADP sensitivity or antioxidant protein content. Combined, these data suggest nitrate supplementation represents a potential therapeutic strategy to attenuate hepatic lipid accumulation and decrease mitochondrial ROS emission following HFD, processes linked to improvements in whole body glucose tolerance. However, the beneficial effects of nitrate within the liver do not appear to be a result of increased oxidative capacity or mitochondrial substrate sensitivity. NEW & NOTEWORTHY The mechanism(s) for how dietary nitrate prevents high-fat diet (HFD)-induced glucose intolerance remain poorly defined. We show that dietary nitrate attenuates HFD-induced increases in lipid accumulation, mitochondrial-specific reactive oxygen species (ROS) emission, and markers of oxidative stress within the liver. The beneficial effects of nitrate were independent of changes 5' AMP-activated protein kinase signaling, mitochondrial content/respiratory capacity, or lipid-supported respiratory sensitivity. Combined, these data provide potential mechanisms underlying the therapeutic potential of dietary nitrate. |
| فهرسة مساهمة: | Keywords: high-fat diet; liver; mitochondria; nitrate; reactive oxygen species |
| المشرفين على المادة: | 0 (Insulin) 0 (Nitrates) 0 (Reactive Oxygen Species) EC 2.7.11.31 (AMP-Activated Protein Kinases) |
| تواريخ الأحداث: | Date Created: 20210707 Date Completed: 20210920 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1152/ajpendo.00610.2020 |
| PMID: | 34229472 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1555 |
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| DOI: | 10.1152/ajpendo.00610.2020 |