bims-kimdis 2023-08-06 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023‒08‒06
fourteen papers selected by
Matías Javier Monsalves Álvarez

Ketolysis drives CD8+ T cell effector function through effects on histone acetylation.
The role of histone deacetylases in NLRP3 inflammasomes-mediated epilepsy.
Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration.
SGLT2 inhibitor canagliflozin alleviates vascular calcification through suppression of NLRP3 inflammasome.
Resistance wheel running improves contractile strength, but not metabolic capacity, in a murine model of volumetric muscle loss injury.
Effects of a high-fat low-carbohydrate diet under different energy conditions on glucose homeostasis and fatty liver development in rats and on gluconeogenesis in the isolated perfused liver.
The interrelationships of diet, body composition and metabolism.
Mitochondrial epigenetics in aging and cardiovascular diseases.
FGF21 promotes myocardial angiogenesis and mediates the cardioprotective effects of exercise in myocardial infarction mice.
Fifty years of research on mitochondrial fatty acid oxidation defects: the remaining challenges.
Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome.
The worsening of skeletal muscle atrophy induced by immobilization at the early stage of remobilization correlates with BNIP3-dependent mitophagy.
Dietary fatty acids activate or deactivate brown and beige fat.
We are what we eat: The role of lipids in metabolic diseases.

Immunity. 2023 Jul 20. pii: S1074-7613(23)00314-X. [Epub ahead of print]

Ketolysis drives CD8+ T cell effector function through effects on histone acetylation.

Katarzyna M Luda, Joseph Longo, Susan M Kitchen-Goosen, Lauren R Duimstra, Eric H Ma, McLane J Watson, Brandon M Oswald, Zhen Fu, Zachary Madaj, Ariana Kupai, Bradley M Dickson, Lisa M DeCamp, Michael S Dahabieh, Shelby E Compton, Robert Teis, Irem Kaymak, Kin H Lau, Daniel P Kelly, Patrycja Puchalska, Kelsey S Williams, Connie M Krawczyk, Dominique Lévesque, François-Michel Boisvert, Ryan D Sheldon, Scott B Rothbart, Peter A Crawford, Russell G Jones.

  Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8+ T cell metabolism and effector function. βOHB directly increased CD8+ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8+ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8+ T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8+ T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.

Keywords:  CD8(+) T cells; TCA cycle; acetyl-CoA; cancer immunology; effector function; epigenetics; ketolysis; ketone bodies; metabolism

DOI:  https://doi.org/10.1016/j.immuni.2023.07.002
Curr Mol Med. 2023 Jul 31.

The role of histone deacetylases in NLRP3 inflammasomes-mediated epilepsy.

Xi Kuang, Shuang Chen, Qingmei Ye.

  Epilepsy is one of the most common brain disorders that not only causes death worldwide, but also affects the daily lives of patients. Previous studies have revealed that inflammation plays an important role in the pathophysiology of epilepsy. Activation of inflammasomes can promote neuroinflammation by boosting the maturation of caspase-1 and the secretion of various inflammatory effectors, including chemokines, interleukins, and tumor necrosis factors. With the in-depth research on the mechanism of inflammasomes in the development of epilepsy, it has been discovered that NLRP3 inflammasomes may induce epilepsy by mediating neuronal inflammatory injury, neuronal loss and blood-brain barrier dysfunction. Therefore, blocking the activation of the NLRP3 inflammasomes may be a new epilepsy treatment strategy. However, the drugs that specifically block NLRP3 inflammasomes assembly has not been approved for clinical use. In this review, the mechanism of how HDACs, an inflammatory regulator, regulates the activation of NLRP3 inflammasome is summarized. It helps to explore the mechanism of the HDAC inhibitors inhibiting brain inflammatory damage so as to provide a potential therapeutic strategy for controlling the development of epilepsy.

Keywords:  Epilepsy; HDACi; Histone deacetylase; NF-?B; NLRP3 Inflammasome; Neuroinflammation

DOI:  https://doi.org/10.2174/1566524023666230731095431
Alzheimers Dement. 2023 Aug 02.

Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration.

Qu Tian, Murat Bilgel, Keenan A Walker, Abhay R Moghekar, Kenneth W Fishbein, Richard G Spencer, Susan M Resnick, Luigi Ferrucci.

  INTRODUCTION: Mitochondrial dysfunction is implicated in the pathophysiology of many chronic diseases. Whether it is related to cognitive impairment and pathological markers is unknown.METHODS: We examined the associations of in vivo skeletal muscle mitochondrial function (post-exercise recovery rate of phosphocreatine [kPCr] via magnetic resonance [MR] spectroscopy with future mild cognitive impairment (MCI) or dementia, and with positron emission tomography (PET) and blood biomarkers of Alzheimer's disease [AD] and neurodegeneration (i.e., Pittsburgh Compound-B [PiB] distribution volume ratio [DVR] for amyloid beta [Aβ], flortaucipir (FTP) standardized uptake value ratio [SUVR] for tau, Aβ42 /40 ratio, phosphorylated tau 181 [p-tau181], neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]).
RESULTS: After covariate adjustment, each standard deviation (SD) higher kPCr level was associated with 52% lower hazards of developing MCI/dementia, and with 59% lower odds of being PiB positive with specific associations in DVR of frontal, parietal, and temporal regions, and cingulate cortex and pallidum. Higher kPCr level was also associated with lower plasma GFAP.
DISCUSSION: In aging, mitochondrial dysfunction may play a vital role in AD pathological changes and neuroinflammation. Highlights Higher in vivo mitochondrial function is related to lower risk of mild cognitive impairment (MCI)/dementia. Higher in vivo mitochondrial function is related to lower amyloid tracer uptake. Higher in vivo mitochondrial function is related to lower plasma neuroinflammation. Mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) and neurodegeneration.

Keywords:  GFAP; PET biomarkers; aging; amyloid; dementia; mitochondrial function; tau

DOI:  https://doi.org/10.1002/alz.13388
Cardiovasc Res. 2023 Jul 31. pii: cvad119. [Epub ahead of print]

SGLT2 inhibitor canagliflozin alleviates vascular calcification through suppression of NLRP3 inflammasome.

An Chen, Zirong Lan, Li Li, Luting Xie, Xiaoyu Liu, Xiulin Yang, Siyi Wang, Qingchun Liang, Qianqian Dong, Liyun Feng, Yining Li, Yuanzhi Ye, Mingwei Fu, Lihe Lu, Jianyun Yan.

  AIMS: Vascular calcification is prevalent in pathological processes such as diabetes, chronic kidney disease (CKD) and atherosclerosis, but effective therapies are still lacking by far. Canagliflozin (CANA), an SGLT2 inhibitor, has been approved for the treatment of type 2 diabetes mellitus and exhibits beneficial effects against cardiovascular disease. However, the effect of CANA on vascular calcification remains unknown. In this study, we hypothesize that CANA protects against vascular calcification.METHODS AND RESULTS: Micro-computed tomography analysis and alizarin red staining revealed that CANA treatment prevented aortic calcification in CKD rats and in VitD3-overloaded mice. Moreover, CANA alleviated calcification of rat and human arterial rings. Alizarin red staining revealed that calcification of rat and human vascular smooth muscle cells (VSMCs) was attenuated by CANA treatment and this phenomenon was confirmed by calcium content assay. In addition, CANA downregulated the expression of osteogenic differentiation markers Runx2 and BMP2. Of interest, qPCR and western blot analysis revealed that CANA downregulated the expression of NLRP3, and the downstream signaling molecules Caspase-1 and IL-1β in VSMCs as well. Both NLRP3 inhibitor MCC950 and knockdown of NLRP3 by siRNA independently resulted in decreased calcification of VSMCs. By contrast, activation of NLRP3 exacerbated VSMC calcification, and this effect was prevented by addition of CANA.
CONCLUSIONS: Our study for the first time demonstrates that CANA exerts a protective effect on vascular calcification at least partially via suppressing NLRP3 signaling pathway. Therefore, supplementation of CANA as well as inhibition of NLRP3 inflammasome presents a potential therapy for vascular calcification.

Keywords:  NLRP3; canagliflozin; chronic kidney disease; vascular calcification; vascular smooth muscle cell

DOI:  https://doi.org/10.1093/cvr/cvad119
Exp Physiol. 2023 Aug 01.

Resistance wheel running improves contractile strength, but not metabolic capacity, in a murine model of volumetric muscle loss injury.

Albino G Schifino, Christiana J Raymond-Pope, Junwon Heo, Jennifer McFaline-Figueroa, Jarrod A Call, Sarah M Greising.

  The primary objective of this study was to determine if low- or high-resistance voluntary wheel running leads to functional improvements in muscle strength (i.e., isometric and isokinetic torque) and metabolic function (i.e., permeabilized fiber bundle mitochondrial respiration) after a volumetric muscle loss (VML) injury. C57BL/6J mice were randomized into one of four experimental groups at age 12 weeks: Uninjured control, VML untreated (VML), low-resistance wheel running (VML-LR), and high-resistance wheel running (VML-HR). All mice, excluding the Uninjured, were subject to a unilateral VML injury to the plantar flexor muscles and wheel running began 3-days post-VML. At 8-weeks post-VML, peak-isometric torque was greater in Uninjured compared to all VML-injured groups, but both VML-LR and VML-HR had greater (∼32%) peak-isometric torque compared to VML. All VML-injured groups had less isokinetic torque compared to Uninjured, and there was no statistical difference among VML, VML-LR, and VML-HR. No differences in cumulative running distance were observed between VML-LR and VML-HR groups. Because adaptations in VML-HR peak-isometric torque were attributed to greater gastrocnemius muscle mass, atrophy- and hypertrophy-related protein content and post-translational modifications were explored via immunoblot; however, results were inconclusive. Permeabilized fiber bundle mitochondrial oxygen consumption was 22% greater in Uninjured compared to VML, but there was no statistical difference among VML, VML-LR, and VML-HR. Furthermore, neither wheel running group demonstrated a change in the relative protein content of the mitochondrial biogenesis transcription factor, PGC-1α. These results indicate that resistance wheel running alone only has modest benefit in the VML-injured muscle. NEW FINDINGS: What is the central question of the study? If initiation of a resistance wheel running regimen following VML improves the functional capacity of skeletal muscle? What is the main finding and its importance? Resistance wheel running led to greater muscle mass and strength in mice with a VML injury but did not result in a full recovery. Neither low- nor high-resistance wheel running was associated with a change in permeabilized muscle fiber respiration despite runners having greater whole-body treadmill endurance capacity, suggesting a resilience to metabolic adaptations in VML-injured muscle. Resistance wheel running may be a suitable adjuvant rehabilitation strategy, but alone does not fully mitigate VML pathology. This article is protected by copyright. All rights reserved.

Keywords:  CK clamp; neuromusculoskeletal injury; rehabilitation; skeletal muscle injury

DOI:  https://doi.org/10.1113/EP091284
Can J Physiol Pharmacol. 2023 Jul 31.

Effects of a high-fat low-carbohydrate diet under different energy conditions on glucose homeostasis and fatty liver development in rats and on gluconeogenesis in the isolated perfused liver.

Mateus José de Oliveira, Evelyn Silva Moreira, Naiara Cristina Lucredi, Carla Indianara Bonetti, Anacharis Babeto de Sá-Nakanishi, Jurandir Fernando Comar, Adelar Bracht, Lívia Bracht.

The beneficial effects of high-fat, low-carbohydrate diets (HFLC) on glucose metabolism have been questioned and its effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of a HFLC diet under different energy conditions on glucose homeostasis, fatty liver development and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for four weeks under three conditions: ad libitum (hypercaloric); isocaloric and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity wasn´t altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver.

DOI: https://doi.org/10.1139/cjpp-2023-0071
Curr Opin Clin Nutr Metab Care. 2023 Sep 01. 26(5): 399-400

The interrelationships of diet, body composition and metabolism.

Manfred J Müller, Dwight E Matthews.

DOI: https://doi.org/10.1097/MCO.0000000000000958
Front Cardiovasc Med. 2023 ;10 1204483

Mitochondrial epigenetics in aging and cardiovascular diseases.

Alessia Mongelli, Alessandro Mengozzi, Martin Geiger, Era Gorica, Shafeeq Ahmed Mohammed, Francesco Paneni, Frank Ruschitzka, Sarah Costantino.

  Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through the oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria-the mitochondrial matrix-contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with genomic DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction. During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory and cardiovascular diseases as well as inflammatory disorders and psychiatric diseases. As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and ROS formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure and ischemia/reperfusion injury. In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases.

Keywords:  aging; cardiovascular diseases; methylation; mitochondria; mitoepigenetics; mtDNA; ncRNAs

DOI:  https://doi.org/10.3389/fcvm.2023.1204483
J Appl Physiol (1985). 2023 Aug 03.

FGF21 promotes myocardial angiogenesis and mediates the cardioprotective effects of exercise in myocardial infarction mice.

Wenyan Bo, Yixuan Ma, Lili Feng, Mengyuan Yu, Lili Zhang, MengXin Cai, Wei Song, Yue Xi, Zhenjun Tian.

  The mechanism by which aerobic exercise promotes cardiac function after myocardial infarction (MI) is still not fully understand. In this study, we investigated the role of fibroblast growth factor 21 (FGF21) in exercise protecting the cardiac function of MI mice. In vivo, MI was induced by left anterior descending coronary artery ligation in wild type and fgf21 knockout mice on the C57BL/6 background. One week after MI, the mice underwent aerobic exercise for 4 weeks. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with H2O2, recombinant human FGF21 (rhFGF21), fibroblast growth factor receptor 1 (FGFR1) inhibitor (PD166866) and phosphatidylinositol3-kinase (PI3K) inhibitor (LY294002) to explore the potential mechanisms. Scratch wound healing and tubule formation analysis were used to detect the migration and tubule formation ability of HUVECs. Our results showed that aerobic exercise significantly promoted angiogenesis and cardiac function through enhancing the expression of FGF21 and activating FGFR1/PI3K/AKT/VEGF pathway. But such beneficial in cardiac from aerobic exercise were attenuated by fgf21 knockout. AICAR enhanced angiogenesis and cell migration through FGF21/FGFR1/PI3K/AKT/VEGF signaling pathway. Under the intervention of H2O2, rhFGF21 also played the role of promoting angiogenesis and cell migration through the same mechanism. In conclusion, our results showed that FGF21 promoted the aerobic exercise-induced angiogenesis and improved cardiac function via FGFR1/PI3K/ AKT/VEGF signal in MI mice.

Keywords:  FGF21; aerobic exercise; angiogenesis; myocardial infraction

DOI:  https://doi.org/10.1152/japplphysiol.00307.2023
J Inherit Metab Dis. 2023 Aug 02.

Fifty years of research on mitochondrial fatty acid oxidation defects: the remaining challenges.

Christine Vianey-Saban, Nathalie Guffon, Alain Fouilhoux, Cécile Acquaviva.

  Since the identification of the first disorder of mitochondrial fatty acid oxidation (FAOD) in 1973, more than twenty defects have been identified. Although there are some differences, most FAOD have similar clinical signs, which are mainly due to energy depletion and toxicity of accumulated metabolites. However, some of them have an unusual clinical phenotype or specific clinical signs. This manuscript focuses on what we have learnt so far on the pathophysiology of these disorders which present with clinical signs that are not typical of categorical FAOD. It also highlights that some disorders have not yet been identified and tries to make assumptions to explain why. It also deals with new treatments under consideration in FAOD, including triheptanoin and similar anaplerotic substrates, ketone body treatments, RNA and gene therapy approaches. Finally, it suggests challenges for the diagnosis of FAOD in the coming years, both for symptomatic patients and for those diagnosed through newborn screening. The ultimate goal would be to identify all the patients born with FAOD and ensure for them the best possible quality of life. TAKE HOME MESSAGE: Tentative hypotheses to improve the diagnosis and the treatment of fatty acid oxidation defects. This article is protected by copyright. All rights reserved.

Keywords:  inborn errors of riboflavin metabolism; mitochondrial fatty acid oxidation disorders

DOI:  https://doi.org/10.1002/jimd.12664
EMBO Mol Med. 2023 Aug 03. e17399

Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome.

Arpita Chowdhury, Angela Boshnakovska, Abhishek Aich, Aditi Methi, Ana Maria Vergel Leon, Ivan Silbern, Christian Lüchtenborg, Lukas Cyganek, Jan Prochazka, Radislav Sedlacek, Jiri Lindovsky, Dominic Wachs, Zuzana Nichtova, Dagmar Zudova, Gizela Koubkova, André Fischer, Henning Urlaub, Britta Brügger, Dörthe M Katschinski, Jan Dudek, Peter Rehling.

  Mitochondria are central for cellular metabolism and energy supply. Barth syndrome (BTHS) is a severe disorder, due to dysfunction of the mitochondrial cardiolipin acyl transferase tafazzin. Altered cardiolipin remodeling affects mitochondrial inner membrane organization and function of membrane proteins such as transporters and the oxidative phosphorylation (OXPHOS) system. Here, we describe a mouse model that carries a G197V exchange in tafazzin, corresponding to BTHS patients. TAZG197V mice recapitulate disease-specific pathology including cardiac dysfunction and reduced oxidative phosphorylation. We show that mutant mitochondria display defective fatty acid-driven oxidative phosphorylation due to reduced levels of carnitine palmitoyl transferases. A metabolic switch in ATP production from OXPHOS to glycolysis is apparent in mouse heart and patient iPSC cell-derived cardiomyocytes. An increase in glycolytic ATP production inactivates AMPK causing altered metabolic signaling in TAZG197V . Treatment of mutant cells with AMPK activator reestablishes fatty acid-driven OXPHOS and protects mice against cardiac dysfunction.

Keywords:  Barth syndrome; cardiolipin; cardiomyopathy; mitochondria; tafazzin

DOI:  https://doi.org/10.15252/emmm.202317399
BMC Musculoskelet Disord. 2023 Aug 04. 24(1): 632

The worsening of skeletal muscle atrophy induced by immobilization at the early stage of remobilization correlates with BNIP3-dependent mitophagy.

Feng Wang, Ting Zhou, Chen Xu Zhou, Quan Bing Zhang, Hua Wang, Yun Zhou.

  BACKGROUND: Recent studies have shown that immobilization enhances reactive oxygen species (ROS) production and mitophagy activity in atrophic skeletal muscle. However, there are relatively few studies examining the biological changes and underlying mechanisms of skeletal muscle during remobilization. In this study, we aimed to investigate the effects of remobilization on skeletal muscle and explore the role of BNIP3-dependent mitophagy in this process.METHODS: Thirty rats were randomly divided into six groups based on immobilization and remobilization time: control (C), immobilization for two weeks (I-2w), and remobilization for one day (R-1d), three days (R-3d), seven days (R-7d), and two weeks (R-2w). At the end of the experimental period, the rectus femoris muscles were removed and weighed, and the measurements were expressed as the ratio of muscle wet weight to body weight (MWW/BW). Sirius Red staining was performed to calculate the values of cross-sectional area (CSA) of rectus femoris. Oxidative fluorescent dihydroethidium was used to evaluate the production of ROS, and the levels of superoxide dismutase (SOD) were also detected. The morphological changes of mitochondria and the formation of mitophagosomes in rectus femoris were examined and evaluated by transmission electron microscope. Immunofluorescence was employed to detect the co-localization of BNIP3 and LC3B, while Western blot analysis was performed to quantify the levels of proteins associated with mitophagy and mitochondrial biogenesis. The total ATP content of the rectus femoris was determined to assess mitochondrial function.
RESULTS: Within the first three days of remobilization, the rats demonstrated decreased MWW/BW, CSA, and ATP concentration, along with increased ROS production and HIF-1α protein levels in the rectus femoris. Results also indicated that remobilization triggered BNIP3-dependent mitophagy, supported by the accumulation of mitophagosomes, the degradation of mitochondrial proteins (including HSP60 and COX IV), the elevation of BNIP3-dependent mitophagy protein markers (including BNIP3, LC3B-II/LC3B-I, and Beclin-1), and the accumulation of puncta representing co-localization of BNIP3 with LC3B. Additionally, PGC-1α, which is involved in the regulation of mitochondrial biogenesis, was upregulated within the first seven days of remobilization to counteract this adverse effect.
CONCLUSION: Our findings suggested that BNIP3-denpendent mitophagy was sustained activated at the early stages of remobilization, and it might contribute to the worsening of skeletal muscle atrophy.

Keywords:  BNIP3-denpendent mitophagy; HIF-1α; Muscle atrophy; ROS; Remobilization

DOI:  https://doi.org/10.1186/s12891-023-06759-2
Life Sci. 2023 Jul 27. pii: S0024-3205(23)00613-6. [Epub ahead of print] 121978

Dietary fatty acids activate or deactivate brown and beige fat.

Min Jia, Tongcheng Xu, Yong-Jiang Xu, Yuanfa Liu.

  Brown adipose tissue (BAT) and beige fat have been documented to rapidly consume fatty acids (FAs) rather than deposit of lipid, and they have high capacity to dissipate energy via nonshivering thermogenesis, making BAT and beige fat potential organs to fight obesity and related chronic diseases. As the main substrate for thermogenesis and the basic constituent unit of triacylglycerol, FAs could modify BAT and remodel white adipose tissue (WAT) to beige fat. However, there are few comprehensive review covering the link between dietary FAs and thermogenic adipocyte..In this review, we described the metabolism of thermogenic adipose upon activation and comprehensively summarized publications on the dietary FAs that activate or deactivate BAT and beige fat. Specifically, eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA), α-linolenic acid (α-ALA), conjugated linoleic acid (CLA), oleic acid (OA), long-chain saturated fatty acid (LC-SFA) and medium-chain fatty acid (MCFA). in addition, the influences on BAT function, WAT remodeling, and lipid metabolism, as well as delineated the possible mechanisms are also reviewed. Characterizing thermogenic or obesogenic dietary FAs may offer novel insight into dietary oil and nutritional treatment.

Keywords:  Brown adipocyte; Dietary fatty acid; Lipid metabolism; Thermogenesis; WAT browning

DOI:  https://doi.org/10.1016/j.lfs.2023.121978
Adv Food Nutr Res. 2023 ;pii: S1043-4526(22)00091-2. [Epub ahead of print]105 173-219

We are what we eat: The role of lipids in metabolic diseases.

Genoveva Berná, Lucía López-Bermudo, Blanca Escudero-López, Franz Martín.

  Lipids play a fundamental role, both structurally and functionally, for the correct functioning of the organism. In the last two decades, they have evolved from molecules involved only in energy storage to compounds that play an important role as components of cell membranes and signaling molecules that regulate cell homeostasis. For this reason, their interest as compounds involved in human health has been gaining weight. Indeed, lipids derived from dietary sources and endogenous biosynthesis are relevant for the pathophysiology of numerous diseases. There exist pathological conditions that are characterized by alterations in lipid metabolism. This is particularly true for metabolic diseases, such as liver steatosis, type 2 diabetes, cancer and cardiovascular diseases. The main issue to be considered is lipid homeostasis. A precise control of fat homeostasis is required for a correct regulation of metabolic pathways and safe and efficient energy storage in adipocytes. When this fails, a deregulation occurs in the maintenance of systemic metabolism. This happens because an increased concentrations of lipids impair cellular homeostasis and disrupt tissue function, giving rise to lipotoxicity. Fat accumulation results in many alterations in the physiology of the affected organs, mainly in metabolic tissues. These alterations include the activation of oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, increased inflammation, accumulation of bioactive molecules and modification of gene expression. In this chapter, we review the main metabolic diseases in which alterations in lipid homeostasis are involved and discuss their pathogenic mechanisms.

Keywords:  Cancer; Cardiovascular diseases; Fat metabolism; Lipid homeostasis; Metabolic diseases; Nonalcoholic fatty liver diseases; Type 2 diabetes mellitus

DOI:  https://doi.org/10.1016/bs.afnr.2022.11.004