Sex modulates hepatic mitochondrial adaptations to high-fat diet and physical activity

The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment of steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator of biogenesis, and BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), a mitophagy regulator, would impact hepatic mitochondrial adaptations (respiratory capacity, H2O2production, mitophagy) to a high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in both sexes. Male and female wild-type (WT), liver-specific PGC-1α heterozygote (LPGC-1α), and BNIP3 null mice were thermoneutral housed (29–31°C) and divided into three groups: sedentary-low-fat diet (LFD), 16 wk of (HFD), or 16 wk of HFD with VWR for the final 8 wk (HFD + VWR) ( n = 5–7/sex/group). HFD did not impair mitochondrial respiratory capacity or coupling in any group; however, HFD + VWR significantly increased maximal respiratory capacity only in WT and PGC-1α females. Males required VWR to elicit mitochondrial adaptations that were inherently present in sedentary females including greater mitochondrial coupling control and reduced H2O2production. Females had overall reduced markers of mitophagy, steatosis, and liver damage. Steatosis and markers of liver injury were present in sedentary male mice on the HFD and were effectively reduced with VWR despite no resolution of steatosis. Overall, reductions in PGC-1α and loss of BNIP3 only modestly impacted mitochondrial adaptations to HFD and HFD + VWR with the biggest effect seen in BNIP3 females. In conclusion, hepatic mitochondrial adaptations to HFD and treatment of HFD-induced steatosis with VWR are more dependent on sex than PGC-1α or BNIP3.

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Less is more? Ultra-low carbohydrate diet and working dogs’ performance

PLoS ONE ◽

10.1371/journal.pone.0261506 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261506

Author(s):

Arnon Gal ◽

Williams Cuttance ◽

Nick Cave ◽

Nicolas Lopez-Villalobos ◽

Aaron Herndon ◽

...

Keyword(s):

Physical Activity ◽

High Fat Diet ◽

Area Under The Curve ◽

Activity Level ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Interstitial Glucose ◽

Working Dogs ◽

Delta G

New Zealand farm working dogs are supreme athletes that are crucial to agriculture in the region. The effects that low or high dietary carbohydrate (CHO) content might have on their interstitial glucose (IG) and activity during work are unknown. The goals of the study were to determine if the concentration of IG and delta-g (a measurement of activity) will be lower in dogs fed an ultra-low CHO high fat diet in comparison to dogs fed a high CHO low fat diet, and to determine if low concentrations of IG are followed by reduced physical activity. We hypothesized that feeding working farm dogs an ultra-low CHO diet would reduce their IG concentrations which in turn would reduce physical activity during work. We prospectively recruited 22 farm dogs from four farms. At each farm, dogs were randomized to one of two diets and had a month of dietary acclimation to their allocated diet. The macronutrient proportions as a percentage of metabolizable energy (%ME) for the high CHO low fat diet (Diet 1) were 23% protein, 25% fat, and 52% CHO, and for the ultra-low CHO high fat diet (Diet 2) 37% protein, 63% fat, and 1% CHO. Following the acclimation period, we continuously monitored IG concentrations with flash glucose monitoring devices, and delta-g using triaxial accelerometers for 96 h. Dogs fed Diet 2 had a lower area under the curve (±SE) for IG (AUC Diet 2 = 497 ± 4 mmol/L/96h, AUC Diet 1 = 590 ± 3 mmol/L/96h; P = 0.002) but a higher area under the curve (±SE) for delta-g (AUC Diet 2 = 104,122 ± 6,045 delta-g/96h, AUC Diet 1 = 80,904 ± 4,950 delta-g/96h; P< 0.001). Interstitial glucose concentrations increased as the activity level increased (P < 0.001) and were lower for Diet 2 within each activity level (P < 0.001). The overall incidence of low IG readings (< 3.5 mmol/L) was 119/3810 (3.12%), of which 110 (92.4%) readings occurred in the Diet 2 group (P = 0.001). In the Diet 2 group, 99/110 (90%) of the low IG events occurred during the resting period (19:00–06:00). We conclude that feeding Diet 2 (ultra-low CHO high fat diet) to working farm dogs was associated with increased delta-g despite decreased IG concentrations. Interstitial glucose concentrations were positively associated with dogs’ activity levels independent of diet. Lastly, events of low IG occurred at a low incidence and were predominantly seen between 19:00–06:00 in dogs fed the ultra-low CHO high fat diet.

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Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-Induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model

International Journal of Molecular Sciences ◽

10.3390/ijms21113983 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3983 ◽

Cited By ~ 1

Author(s):

Islam N. Mohamed ◽

Nader Sheibani ◽

Azza B. El-Remessy

Keyword(s):

Adhesion Molecules ◽

Nlrp3 Inflammasome ◽

High Fat Diet ◽

Receptor Protein ◽

Inflammasome Activation ◽

High Fat ◽

Barrier Dysfunction ◽

Interacting Protein ◽

Thioredoxin Interacting Protein ◽

The Impact

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8–18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood–retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1β in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1β, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1β receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation.

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Daily physical activity and macronutrient distribution of low-calorie diets jointly affect body fat reduction in obese women

Applied Physiology Nutrition and Metabolism ◽

10.1139/h09-015 ◽

2009 ◽

Vol 34 (4) ◽

pp. 595-602 ◽

Cited By ~ 4

Author(s):

Constanza Matilde López-Fontana ◽

Almudena Sánchez-Villegas ◽

Miguel Angel Martínez-Gonzalez ◽

José Alfredo Martinez

Keyword(s):

Physical Activity ◽

Body Composition ◽

Body Fat ◽

High Fat Diet ◽

Fat Distribution ◽

Obese Women ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Composition Changes

Inadequate dietary patterns and sedentary lifestyles are believed to be important factors in predisposing people to obesity. This study analyzed the potential interaction between habitual physical activity and the carbohydrate (CHO)-fat distribution in 2 hypocaloric diets and the impact of such interplay on body composition changes. Forty healthy obese women, 20–50 years old, were randomly assigned to a high- or low-CHO energy-restricted diet, which was low or high in fat, respectively, during 10 weeks. Baseline and final measurements were performed to assess dietary habits, resting metabolic rate, and body composition changes. Physical activity was measured with a triaxial accelerometer and with a questionnaire. There were no significant differences in anthropometric and metabolic variables between both dietary groups at baseline. However, there was a positive correlation between total free-living physical activity and arm muscle preservation after 10 weeks (r = 0.371; p = 0.024). Interestingly, an interaction between macronutrient (CHO–fat distribution) intake and physical activity was found, since less-active subjects with a high-CHO–low-fat diet showed a greater fat loss than those more active with a lower-CHO–high-fat diet, whereas more-active subjects with a high-CHO–low-fat diet showed a smaller fat loss than those receiving a low-CHO–high-fat diet. Physical activity and the macronutrient content of energy-restricted diets, when designed to promote body fat mass reduction, should be considered together to better predict the outcome.

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Impact of APOE Genotype on Diet-induced Mitochondrial Adaptations in Mouse Skeletal Muscle

Innovation in Aging ◽

10.1093/geroni/igab046.3491 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 979-979

Author(s):

Niaya James ◽

Oyinkansola Shonde ◽

Nahdia Jones ◽

G William Rebeck ◽

Joanne Allard ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

High Fat Diet ◽

Motor Coordination ◽

Wheel Running ◽

Apoe Genotype ◽

Peroxisome Proliferator ◽

High Fat ◽

Western Blots ◽

The Impact

Abstract Apolipoprotein E (APOE), a component of lipoproteins that facilitates cholesterol transportation, has three variants in the human genome: APOE2, E3, and E4. Prior research found that carriers of APOE4 are more susceptible to developing Alzheimer's disease (AD) and other brain disorders than those who possess other APOE alleles, and that these carriers are also predisposed to mitochondrial impairment– an early characteristic of neuronal dysfunction. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1ɑ) is a major biomarker for mitochondrial biogenesis and function and cytochrome c oxidase subunit IV (COX4) is the terminal enzyme of the mitochondrial respiratory chain. Decreased measures of these proteins indicate reduced mitochondrial function. Aside from genetic inheritance, lifestyle factors such as diet and exercise significantly impact one’s risk for mitochondrial dysfunction and AD. In these studies, we examined the impact of APOE variance on physiological adaptations induced by either exercise or a high-fat diet, with a focus on biomarkers of mitochondrial function. Western blots were used to measure COX4 and PGC-1ɑ levels in skeletal muscle tissue from female APOE3 and APOE4 knock-in transgenic mice. Based on performance on a motorized rotating rod and voluntary wheel-running, we deduced that female APOE4 mice exhibit reduced motor coordination and activity relative to APOE3 mice. APOE4 mice also had reduced COX4 levels that were increased by the high-fat diet. In contrast, COX4 levels in APOE3 mice were reduced in the high-fat diet group. Our data show that diet and APOE genotype interact to produce adaptations in mitochondrial proteins in skeletal muscle.

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Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642518 ◽

1994 ◽

Vol 71 (06) ◽

pp. 755-758 ◽

Cited By ~ 46

Author(s):

E M Bladbjerg ◽

P Marckmann ◽

B Sandström ◽

J Jespersen

Keyword(s):

High Fat Diet ◽

Fat Content ◽

Factor Vii ◽

Amidolytic Activity ◽

High Fat ◽

Low Fat Diet ◽

Increased Risk ◽

Coagulant Activity ◽

High Fat Diets ◽

Fat Diets

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.

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The impact of High Fat Diet on bone: potential mechanisms

Food & Function ◽

10.1039/d0fo02664f ◽

2021 ◽

Author(s):

Qiao Jie ◽

Yue-Zhong Ren ◽

Yi-wen Wu

Keyword(s):

Total Energy ◽

High Fat Diet ◽

High Fat ◽

High Fat Diets ◽

Fat Diets ◽

The Impact

High-fat diets(HFD)are defined as lipids accounting for exceeded 30% of total energy in-take, and current research is mostly 45% and 60%. With a view of the tendency that patients who...

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Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00102.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. G510-G516

Author(s):

Karin E. R. Gooijert ◽

Rick Havinga ◽

Alida R. Oosterloo-Duinkerken ◽

Enge E. A. Venekamp-Hoolsema ◽

Folkert Kuipers ◽

...

Keyword(s):

High Fat Diet ◽

Fecal Excretion ◽

High Fat ◽

Erythropoietic Protoporphyria ◽

Low Fat Diet ◽

Fecal Fat ◽

Sucrose Polyesters ◽

Hydrophobic Compound ◽

Fat Excretion ◽

Stimulation Of

Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient ( fch/ fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/ fch mice. Fch/ fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/ fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/ fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.

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