Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity

Sacks, Jessica; Mulya, Anny; Fealy, Ciaràn E.; Huang, Hazel; Mosinski, J. David; Pagadala, Mangesh; Shimizu, Hiroki; Batayyah, Esam; Schauer, Philip R.; Brethauer, Stacy A.; Kirwan, John P.

doi:10.14814/phy2.13600

Cited by 26 publications

(19 citation statements)

References 57 publications

(129 reference statements)

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“…A disturbed balance between fusion and fission, based on gene expression levels of involved proteins in skeletal muscle, has been identified in ageing, obesity and type 2 diabetes [ 10 , 11 ]. In addition, it has been shown that fusion and fission proteins respond to lifestyle interventions such as caloric restriction, physical activity [ 12 , 13 ] and following Roux-en-Y gastric bypass (RYGB) surgery in rats [ 14 ]. Few studies have examined the mitochondrial network in human skeletal muscle [ 15 , 16 ], especially in relation to insulin resistance and mild obesity.…”

Section: Introductionmentioning

confidence: 99%

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

et al. 2020

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Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity. Methods In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n = 11), obese participants without diabetes (n = 12), lean individuals (n = 10) and endurance-trained athletes (n = 12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue. Results Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6 ± 4.0 and 56.7 ± 7.2 vs 21.8 ± 2.5 and 25.1 ± 4.3 years, p < 0.001, respectively) and displayed a higher BMI (32.4 ± 3.7 and 31.0 ± 3.7 vs 22.1 ± 1.8 and 21.0 ± 1.5 kg/m2, p < 0.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86 ± 0.79 vs 0.79 ± 0.51 AU, p = 0.002; and OPA1: 1.55 ± 0.64 vs 0.76 ± 0.52 AU, p = 0.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (n = 6). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (p = 0.048) and type 2 diabetes (p = 0.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (r = 0.48, p = 0.0001; r = 0.55, p < 0.001 and r = 0.61, p < 0.0001, respectively) and insulin sensitivity (r = 0.40, p = 0.008; r = 0.44, p = 0.003 and r = 0.48, p = 0.001, respectively). Conclusions/interpretation Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity. Clinical Trial registry numbers NCT00943059, NCT01298375 and NL1888

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Section: Introductionmentioning

confidence: 99%

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

et al. 2020

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“…[1][2][3][4][5][6] Triggers, such as hyperglycemia, can induce increased intracellular reactive oxygen species (ROS). [1][2][3][4][5][6][7] Surprisingly, bariatric surgery-induced weight loss has been shown to improve mitochondrial biogenesis, whereas diet-induced weight reduction did not improve mitochondrial dysfunction. 4 Moreover, bariatric surgery may be associated with improved renal tubular injury, which is determined via monitoring the level of kidney injury molecule-1 in patients with obesity.…”

Section: Introductionmentioning

confidence: 99%

Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Seo

Kim

Noh

et al. 2020

BMJ Open Diab Res Care

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IntroductionRecent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date.Research design and methodsWe prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery.ResultsThe copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM.ConclusionThese results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.

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“…The previously mentioned studies all examined fasting on normal, healthy rodents; however, Sacks et al 66 . assess gastric bypass surgery in obese animals and the effect this has on mitochondrial dynamics.…”

Section: Resultsmentioning

confidence: 99%

“…The previously mentioned studies all examined fasting on normal, healthy rodents; however, Sacks et al 66 assess gastric bypass surgery in obese animals and the effect this has on mitochondrial dynamics. Rats (12 weeks of age) were placed on a high-fat diet to establish obesity and then divided into sham surgery or ROX-en-Y gastric bypass surgery (RYGB).…”

Section: Fasting or Calorie Restriction And Mitophagymentioning

confidence: 99%

The effect of fasting or calorie restriction on mitophagy induction: a literature review

Mehrabani

Bagherniya

Askari

et al. 2020

J cachexia sarcopenia muscle

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Mitochondrial dysfunction can be a major cause of a wide range of age-related diseases. Maintaining the normal homeostasis of mitochondria population plays an important role in ensuring people's health, which is done through the mitophagy process. Among the various stimuli for the onset of mitophagy, caloric restriction (CR) is one of the strongest non-genetic triggers for initiating the mitophagy process. The primary objective of this paper is to review the literature assessing the effect of CR on mitophagy. Medline, Web of Science, Scopus, and Google Scholar databases was searched from inception to 1 August 2019. Reference lists from all selected articles were also examined for additional relevant studies. The evidence regarding the effect of fasting or CR on mitophagy is still limited. In addition, the methodological approaches of the studies are too heterogeneous in terms of types of food restriction, study duration, and targeted tissues. Most of the studies showed that fasting or CR induced mitophagy and mitophagy-related markers such as Binp3 and Parkin. However, some studies demonstrated that mitophagy occurred both in fasting and fed state with no significant differences or may be induced in fed state. Study on the muscle tissue of subjects after exercise showed that mitophagy was upregulated in the fed state. It has been demonstrated that mitophagy in the muscle was lowered in the absence of AMP-dependent kinase and fibroblast growth factor 21 genes, both in fasted and fed conditions. Current evidence overwhelmingly suggests that CR and fasting induce mitophagy and mitophagy-related markers. Based on the current evidence that we reviewed here, it could be concluded that fasting or CR has a promising role as a novel and practical approach in the prevention of age-related diseases without any side effects by inducing mitophagy in different organs of the body. More studies will be required in future to clarify the relationship between food deprivation and mitophagy. Further studies using a variety of different types of CR and fasting states are also warranted to determine the best approach for inducing mitophagy and improving health.

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Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity

Cited by 26 publications

References 57 publications

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

The effect of fasting or calorie restriction on mitophagy induction: a literature review

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