scholarly journals Skeletal Muscle Mitochondrial Respiration Is Elevated in Female Cynomolgus Macaques Fed a Western Compared with a Mediterranean Diet

2019 ◽  
Vol 149 (9) ◽  
pp. 1493-1502 ◽  
Author(s):  
Jenny L Gonzalez-Armenta ◽  
Zhengrong Gao ◽  
Susan E Appt ◽  
Mara Z Vitolins ◽  
Kristofer T Michalson ◽  
...  

ABSTRACT Background Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with limited evidence for causation or animal studies focused on single macro- or micronutrients; therefore, primate animal models provide an opportunity to determine potential mechanisms underlying the effects of dietary patterns on health and disease. Objective The aim of this study was to determine the effects of whole dietary patterns, either a Western or Mediterranean diet, on skeletal muscle mitochondrial bioenergetics in cynomolgus macaques. Methods In this study, 22 adult female cynomolgus macaques (∼11–14 y by dentition) were fed either a Western or Mediterranean diet for 30 mo. The Western diet was designed to mimic the diet of a middle-aged American woman and the Mediterranean diet included key aspects of Mediterranean diets studied in humans, such as plant-based proteins and fat, complex carbohydrates, and fiber. Diets were matched on macronutrient composition (16% protein, 54% carbohydrate, and 31% fat) and cholesterol content. Skeletal muscle was collected for high-resolution respirometry, citrate synthase activity, and western blot measurements. Pearson correlation analysis between respirometry measures and measures of carbohydrate metabolism was also performed. Results We found that consumption of a Western diet resulted in significantly higher mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO + complex I (52%), complex I + II (31%), max electron transport system (ETS) (31%), and ETS rotenone sensitive (31%) than did consumption of a Mediterranean diet. In addition, measures of respiration in response to fatty acids were significantly and positively correlated with both insulin resistance and plasma insulin concentrations. Conclusions This study highlights the importance of dietary composition in mitochondrial bioenergetics and that diet can influence skeletal muscle mitochondrial respiration independently of other factors such as macronutrient composition.

Author(s):  
K. Allison Amick ◽  
Gargi Mahapatra ◽  
Jaclyn Bergstrom ◽  
Zhengrong Gao ◽  
Suzanne Craft ◽  
...  

Mitochondrial dysfunction is evident in diseases affecting cognition and metabolism such as Alzheimer's disease and type 2 diabetes. Human studies of brain mitochondrial function are limited to post-mortem tissue, preventing the assessment of bioenergetics by respirometry. Here, we investigated the effect of two diets on mitochondrial bioenergetics in three brain regions: the prefrontal cortex (PFC), the entorhinal cortex (ERC), and the cerebellum (CB), using middle-aged non-human primates. Eighteen female cynomolgus macaques aged 12.3 ± 0.7 years were fed either a Mediterranean diet that is associated with healthy outcomes or a Western diet that is associated with poor cognitive and metabolic outcomes. Average bioenergetic capacity within each brain region did not differ between diets. Distinct brain regions have different metabolic requirements related to their function and disease susceptibility. Therefore, we also examined differences in bioenergetic capacity between brain regions. Mitochondria isolated from animals fed a Mediterranean diet maintained distinct differences in mitochondrial bioenergetics between brain regions while animals fed the Western diet had diminished distinction in bioenergetics between brain regions. Notably, fatty acid β-oxidation was not affected between regions in animals fed a Western diet. Additionally, bioenergetics in animals fed a Western diet had positive associations with fasting blood glucose and insulin levels in PFC and ERC mitochondria, but not in CB mitochondria. Altogether, these data indicate that a Western diet disrupts bioenergetics across brain regions and that circulating blood glucose and insulin levels in Western diet fed animals influence bioenergetics in brain regions susceptible to Alzheimer's disease and type 2 diabetes.


2017 ◽  
Vol 123 (6) ◽  
pp. 1516-1524 ◽  
Author(s):  
Adam R. Konopka ◽  
William M. Castor ◽  
Christopher A. Wolff ◽  
Robert V. Musci ◽  
Justin J. Reid ◽  
...  

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s−1·mg tissue−1) and ETS (231 pmol·s−1·mg tissue−1) capacities that rank among the highest published to date in humans. Mitochondrial (3.2-fold), cytoplasmic (2.3-fold), and myofibrillar (1.5-fold) protein synthesis rates were greater during CTR compared with CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (−12 and −14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (−26 and −31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics. NEW & NOTEWORTHY The mechanisms that maintain skeletal muscle function during extreme stresses remain incompletely understood. In the current study, greater rates of mitochondrial protein synthesis during the energetic demands of ultra-endurance exercise may contribute to rapid adaptations in mitochondrial bioenergetics. The endurance athlete herein achieved mitochondrial respiratory capacities among the highest published for humans. Greater mitochondrial protein synthesis during ultra-endurance exercise may contribute to improved mitochondrial respiration and serve as a mechanism to resist cellular energetic stresses.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2565 ◽  
Author(s):  
Tiffany M. Newman ◽  
Mara Z. Vitolins ◽  
Katherine L. Cook

Diet is a modifiable component of lifestyle that could influence breast cancer development. The Mediterranean dietary pattern is considered one of the healthiest of all dietary patterns. Adherence to the Mediterranean diet protects against diabetes, cardiovascular disease, and cancer. Reported consumption of a Mediterranean diet pattern was associated with lower breast cancer risk for women with all subtypes of breast cancer, and a Western diet pattern was associated with greater risk. In this review, we contrast the available epidemiological breast cancer data, comparing the impact of consuming a Mediterranean diet to the Western diet. Furthermore, we will review the preclinical data highlighting the anticancer molecular mechanism of Mediterranean diet consumption in both cancer prevention and therapeutic outcomes. Diet composition is a major constituent shaping the gut microbiome. Distinct patterns of gut microbiota composition are associated with the habitual consumption of animal fats, high-fiber diets, and vegetable-based diets. We will review the impact of Mediterranean diet on the gut microbiome and inflammation. Outside of the gut, we recently demonstrated that Mediterranean diet consumption led to distinct microbiota shifts in the mammary gland tissue, suggesting possible anticancer effects by diet on breast-specific microbiome. Taken together, these data support the anti-breast-cancer impact of Mediterranean diet consumption.


2020 ◽  
Vol 21 (17) ◽  
pp. 6255
Author(s):  
Chase M. Walton ◽  
Samuel M. Jacobsen ◽  
Blake W. Dallon ◽  
Erin R. Saito ◽  
Shantelle L. H. Bennett ◽  
...  

Objective: The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Energy expenditure has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The central aim of this study was to explore the effects of the ketone β-hydroxybutyrate (βHB) on mitochondrial bioenergetics in adipose tissue. Methods: We employed three distinct systems—namely, cell, rodent, and human models. Following exposure to elevated βHB, we obtained adipose tissue to quantify mitochondrial function. Results: In every model, βHB robustly increased mitochondrial respiration, including an increase of roughly 91% in cultured adipocytes, 113% in rodent subcutaneous adipose tissue (SAT), and 128% in human SAT. However, this occurred without a commensurate increase in adipose ATP production. Furthermore, in cultured adipocytes and rodent adipose, we quantified and observed an increase in the gene expression involved in mitochondrial biogenesis and uncoupling status following βHB exposure. Conclusions: In conclusion, βHB increases mitochondrial respiration, but not ATP production, in mammalian adipocytes, indicating altered mitochondrial coupling. These findings may partly explain the increased metabolic rate evident in states of elevated ketones, and may facilitate the development of novel anti-obesity interventions.


2020 ◽  
Vol 318 (1) ◽  
pp. E44-E51 ◽  
Author(s):  
Cynthia M. F. Monaco ◽  
Catherine A. Bellissimo ◽  
Meghan C. Hughes ◽  
Sofhia V. Ramos ◽  
Robert Laham ◽  
...  

Sexual dimorphism in mitochondrial respiratory function has been reported in young women and men without diabetes, which may have important implications for exercise. The purpose of this study was to determine if sexual dimorphism exists in skeletal muscle mitochondrial bioenergetics in people with type 1 diabetes (T1D). A resting muscle microbiopsy was obtained from women and men with T1D ( n = 10/8, respectively) and without T1D (control; n = 8/7, respectively). High-resolution respirometry and spectrofluorometry were used to measure mitochondrial respiratory function, hydrogen peroxide (mH2O2) emission and calcium retention capacity (mCRC) in permeabilized myofiber bundles. The impact of T1D on mitochondrial bioenergetics between sexes was interrogated by comparing the change between women and men with T1D relative to the average values of their respective sex-matched controls (i.e., delta). These aforementioned analyses revealed that men with T1D have increased skeletal muscle mitochondrial complex I sensitivity but reduced complex II sensitivity and capacity in comparison to women with T1D. mH2O2 emission was lower in women compared with men with T1D at the level of complex I (succinate driven), whereas mCRC and mitochondrial protein content remained similar between sexes. In conclusion, women and men with T1D exhibit differential responses in skeletal muscle mitochondrial bioenergetics. Although larger cohort studies are certainly required, these early findings nonetheless highlight the importance of considering sex as a variable in the care and treatment of people with T1D (e.g., benefits of different exercise prescriptions).


2020 ◽  
pp. 1-10
Author(s):  
M.S. Davis ◽  
M.R. Fulton ◽  
A. Popken

The skeletal muscle of exercising horses develops pronounced hyperthermia and acidosis during strenuous or prolonged exercise, with very high tissue temperature and low pH associated with muscle fatigue or damage. The purpose of this study was to evaluate the individual effects of physiologically relevant hyperthermia and acidosis on equine skeletal muscle mitochondrial function, using ex vivo measurement of oxygen consumption to assess the function of different mitochondrial elements. Fresh triceps muscle biopsies from 6 healthy unfit Thoroughbred geldings were permeabilised to permit diffusion of small molecular weight substrates through the sarcolemma and analysed in a high resolution respirometer at 38, 40, 42, and 44 °C, and pH=7.1, 6.5, and 6.1. Oxygen consumption was measured under conditions of non-phosphorylating (leak) respiration and phosphorylating respiration through Complex I and Complex II. Data were analysed using a one-way repeated measures ANOVA and data are expressed as mean ± standard deviation. Leak respiration was ~3-fold higher at 44 °C compared to 38 °C regardless of electron source (Complex I: 22.88±3.05 vs 8.08±1.92 pmol O2/mg/s), P=0.002; Complex II: 79.14±23.72 vs 21.43±11.08 pmol O2/mg/s, P=0.022), resulting in a decrease in efficiency of oxidative phosphorylation. Acidosis had minimal effect on mitochondrial respiration at pH=6.5, but pH=6.1 resulted in a 50% decrease in mitochondrial oxygen consumption. These results suggest that skeletal muscle hyperthermia decreases the efficiency of oxidative phosphorylation through increased leak respiration, thus providing a specific biochemical basis for hyperthermia-induced muscle fatigue. The effect of myocellular acidosis on mitochondrial respiration was minimal under typical levels of acidosis, but atypically severe acidosis can lead to impairment of mitochondrial function.


2020 ◽  
Vol 21 ◽  
pp. 100717 ◽  
Author(s):  
Satoshi Maekawa ◽  
Shingo Takada ◽  
Takaaki Furihata ◽  
Arata Fukushima ◽  
Takashi Yokota ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Christine N. El Khoury ◽  
Sofi G. Julien

Background: Since 2019, the world is confronting the COVID-19 public health crisis that deeply impacted all aspects of life, from the health sector to economy. Despite the advancement of research targeting pandemic containment measures, more strategies are still needed to alleviate the burden caused by this novel disease. In particular, optimal nutrition was proposed as a possible mitigating factor in the context of COVID-19. Indeed, the light is shed on balanced diets, such as the Mediterranean diet, which present the finest nutritional quality to support the immune system and other physiologic functions. In contrast, less varied diets that lack the needed nutrients and favor inflammation have been correlated with adverse health effects, including a hindered immune response, such as the western diet.Methods: This observational case control study aimed at exploring the possible associations between the different dietary patterns present among a sample of the Lebanese population and the COVID-19 occurrence and outcomes. An online survey collected information about the sociodemographic characteristics, health status, lifestyle, and dietary habits through the Mediterranean diet questionnaire and a semi-quantitative fod frequency questionnaire, and the COVID-19 infection and its burden. The sample consisted of 399 respondents divided into the case and control groups (37.6 and 62.4%, respectively) on the basis of the presence or absence of a COVID-19 infection history.Results: The participants in the case and control groups had average adherence to the Mediterranean diet and their dietary intake was closer to the western diet. However, the cases had a lower mean of the MedDiet score (p = 0.009). Food groups consumption analysis showed that this significant difference within the overall similar dietary patterns was due to a higher consumption of poultry and a trend toward decreased consumption of olive oil and increased read meat and alcohol intake among the cases. Additionally, gender influenced the levels of different foods' consumption. Nonetheless, the dietary intake did not impact the COVID-19 burden.Conclusion: It is recommended to adopt healthy food choices within the different dietary patterns for a better protection against COVID-19. These findings should be validated in larger-scale studies.


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