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Background: Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota., Methods and Findings: A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n 2 p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study., Conclusions: We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials., Trial Registration: This trial was registered with ClinicalTrials.gov (NCT05200468)., Competing Interests: Declaration of conflict of interest Laura A. Velázquez-Villegas received research funding from Laboratorios Senosiain S.A. de C.V., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The increase in incidence and prevalence of metabolic diseases, such as diabetes, obesity, and metabolic syndrome, is a health problem worldwide. Nutritional strategies that can impact on mitochondrial activity represent a novel and effective option to modulate energy expenditure and energetic metabolism in cells and tissues and could be used as adjuvant treatments for metabolic-associated disorders. Dietary bioactive compounds also known as "food bioactives" have proven to exert multiple health benefits and counteract metabolic alterations. In the last years, it has been consistently reported that the modulation of mitochondrial function represents one of the mechanisms behind the bioactive compounds-dependent health improvements. In this review, we focus on gathering, summarizing, and discussing the evidence that supports the effect of dietary bioactive compounds on mitochondrial activity and the relation of these effects in the pathological context. Despite the evidence presented here on in vivo and in vitro effects, more studies are needed to determine their effectiveness in humans., (Copyright © 2021. Published by Elsevier Inc.)

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome.

Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD+-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant protein desuccinylase and demalonylase in the mitochondria because the ablation of Sirt5 enhanced the global succinylation and malonylation of mitochondrial proteins, including many metabolic enzymes. In order to determine the physiological role of Sirt5 in metabolic homeostasis, we generated a germline Sirt5 deficient (Sirt5-/-) mouse model and performed a thorough metabolic characterization of this mouse line. Although a global protein hypersuccinylation and elevated serum ammonia during fasting were observed in our Sirt5-/- mouse model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under either chow or high fat diet conditions. These observations suggest that Sirt5 is likely to be dispensable for the metabolic homeostasis under the basal conditions [ABSTRACT FROM AUTHOR]

Omega-3 fatty acids (w-3 FA) have anti-inflammatory effects and improve mitochondrial function. Nonetheless, little is known about their effect on mitochondrial bioenergetics of peripheral blood mononuclear cells (PBMCs) in individuals with obesity. Thus, this study aimed to determine the mitochondrial bioenergetics status and cell subset composition of PBMCs during obesity, before and after 1 month supplementation with w-3 FA. We performed a case-control study with twelve women with normal BMI (lean group) and 19 with grade 2 obesity (obese group), followed by a before-after prospective study where twelve subjects with obesity received a 1 month intervention with 5.25 g of w-3 FA (3.5 g eicosapentaenoic (EPA) and 1.75 g docosahexaenoic (DHA) acids), and obtained PBMCs from all participants. Mitochondrial bioenergetic markers, including basal and ATP-production associated respiration, proton leak, and nonmitochondrial respiration, were higher in PBMCs from the obese group vs. the lean group. The bioenergetic health index (BHI), a marker of mitochondrial function, was lower in the obese vs. the lean group. In addition, Th1, Th2, Th17, CD4+ Tregs, CD8+ Tregs, and Bregs, M1 monocytes and pDCreg cells were higher in PBMCs from the obese group vs. the lean group. The w-3 FA intervention improved mitochondrial function, mainly by decreasing nonmitochondrial respiration and increasing the reserve respiratory capacity and BHI. The intervention also reduced circulating pro-inflammatory and anti-inflammatory lymphocyte and monocytes subsets in individuals with obesity. The mitochondrial dysfunction of PBMCs and the higher proportion of peripheral pro-inflammatory and anti-inflammatory immune cells in subjects with obesity, improved with 1 month supplementation with EPA and DHA. [Display omitted] [ABSTRACT FROM AUTHOR]