scholarly journals Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics

2020 ◽  
Vol 21 (17) ◽  
pp. 6255
Author(s):  
Chase M. Walton ◽  
Samuel M. Jacobsen ◽  
Blake W. Dallon ◽  
Erin R. Saito ◽  
Shantelle L. H. Bennett ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Mitochondrial Bioenergetics ◽  
Human Metabolism ◽  
Macronutrient Composition ◽  
Atp Production ◽  
Ketogenic Diets ◽  
Low Carbohydrate ◽  
Obesity Interventions ◽  
Subcutaneous Adipose

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.

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 ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mediterranean Diet ◽  
Dietary Patterns ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Western Diet ◽  
Cardiometabolic Health ◽  
Mitochondrial Bioenergetics ◽  
Macronutrient Composition ◽  
Cynomolgus Macaques

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.

scholarly journals Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Christoph Hoffmann ◽  
Patrick Schneeweiss ◽  
Elko Randrianarisoa ◽  
Günter Schnauder ◽  
Lisa Kappler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Respiration ◽  
Subcutaneous Adipose Tissue ◽  
Muscle Fibers ◽  
Sensitivity Index ◽  
Respiratory Capacity ◽  
Subcutaneous Adipose

Abstract Context Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. Objective To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Design Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Results Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Conclusion Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

scholarly journals Biological characteristics and metabolic profile of canine mesenchymal stem cells isolated from adipose tissue and umbilical cord matrix

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247567
Author(s):  
Romina Marcoccia ◽  
Salvatore Nesci ◽  
Barbara Merlo ◽  
Giulia Ballotta ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Production Rate ◽  
Umbilical Cord ◽  
Mitochondrial Respiration ◽  
Companion Animals ◽  
Differentiation Potential ◽  
Atp Production ◽  
Umbilical Cord Matrix

Despite the increasing demand of cellular therapies for dogs, little is known on the differences between adult and fetal adnexa canine mesenchymal stem cells (MSCs), and data on their metabolic features are lacking. The present study aimed at comparing the characteristics of canine adipose tissue (AT) and umbilical cord matrix (UC) MSCs. Moreover, for the first time in the dog, the cellular bioenergetics were investigated by evaluating the two main metabolic pathways (oxidative phosphorylation and glycolysis) of ATP production. Frozen-thawed samples were used for this study. No differences in mean cell proliferation were found (P>0.05). However, while AT-MSCs showed a progressive increase in doubling time over passages, UC-MSCs showed an initial post freezing-thawing latency. No differences in migration, spheroid formation ability, and differentiation potential were found (P>0.05). RT-PCR analysis confirmed the expression of CD90 and CD44, the lack of CD14 and weak expression of CD34, mostly by AT-MSCs. DLA-DRA1 and DLA-DQA1 were weakly expressed only at passage 0 by UC-MSCs, while they were expressed at different passages for AT-MSCs. There was no difference (P>0.05) in total ATP production between cell cultures, but the ratio between the “mitochondrial ATP Production Rate” and the “glycolytic ATP Production Rate” was higher (P<0.05) in AT- than in UC-MSCs. However, in both MSCs types the mitochondrial respiration was the main pathway of ATP production. Mitochondrial respiration and ATP turnover in UC-MSCs were higher (P<0.05) than in AT-MSCs, but both had a 100% coupling efficiency. These features and the possibility of increasing the oxygen consumption by a spare respiratory capacity of four (AT-MSCSs) and two (UC-MSCs) order of magnitude greater than basal respiration, can be taken as indicative of the cell propensity to differentiate. The findings may efficiently contribute to select the most appropriate MSCs, culture and experimental conditions for transplantation experiments in mesenchymal stem cell therapy for companion animals.

scholarly journals Transporter-Mediated Mitochondrial GSH Depletion Leading to Mitochondrial Dysfunction and Rescue with αB Crystallin Peptide in RPE Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 411
Author(s):  
Parameswaran G Sreekumar ◽  
Mo Wang ◽  
Christine Spee ◽  
Srinivas R. Sadda ◽  
Ram Kannan
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Barrier Function ◽  
Mitochondrial Bioenergetics ◽  
Rpe Cells ◽  
Atp Production ◽  
Αb Crystallin ◽  
Mitochondrial Glutathione

Mitochondrial glutathione (mGSH) is critical for cell survival. We recently reported the localization of OGC (SLC25A11) and DIC (SLC25A10) in hRPE. Herein, we investigated the suppression of OGC and DIC and the effect of αB crystallin chaperone peptide co-treatment on RPE cell death and mitochondrial function. Non-polarized and polarized human RPE were co-treated for 24 h with phenyl succinic acid (PS, 5 mM) or butyl malonic acid (BM, 5 mM) with or without αB cry peptide (75 µg/mL). mGSH levels, mitochondrial bioenergetics, and ETC proteins were analyzed. The effect of mGSH depletion on cell death and barrier function was determined in polarized RPE co-treated with PS, OGC siRNA or BM and αB cry peptide. Inhibition of OGC and DIC resulted in a significant decrease in mGSH and increased apoptosis. mGSH depletion significantly decreased mitochondrial respiration, ATP production, and altered ETC protein expression. αB cry peptide restored mGSH, attenuated apoptosis, upregulated ETC proteins, and improved mitochondrial bioenergetics and biogenesis. mGSH transporters exhibited differential polarized localization: DIC (apical) and OGC (apical and basal). Inhibition of mGSH transport compromised barrier function which was partially restored by αB cry peptide. Our findings suggest mGSH augmentation by its transporters may be a valuable approach in AMD therapy.

Insulin resistance, systemic and regional inflammation in subcutaneous adipose tissue during weight loss in a population with obesity

2019 ◽  
Author(s):  
Frederique Van de Velde ◽  
Margriet Ouwens ◽  
Arsene-Helene Batens ◽  
Samyah Shadid ◽  
Bruno Lapauw ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Subcutaneous Adipose

701-P: Effects of Exercise on Extracellular Matrix Modifiers in Subcutaneous Adipose Tissue of Obese Adults

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 701-P
Author(s):  
PALLAVI VARSHNEY ◽  
BENJAMIN J. RYAN ◽  
CHIWOON AHN ◽  
MICHAEL W. SCHLEH ◽  
JEFFREY F. HOROWITZ
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Obese Adults ◽  
Subcutaneous Adipose
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