Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats

Low birth weight is associated with an increased risk for developing type 2 diabetes and metabolic diseases. The placental capacity to supply nutrients and oxygen to the fetus represents the main determiner of fetal growth. However, few studies have investigated the effects of maternal diet on the placenta. We explored placental adaptive proteomic processes implicated in response to maternal undernutrition. Rat term placentas from 70% food-restricted (FR30) mothers were used for a proteomic screen. Placental mitochondrial functions were evaluated using molecular and functional approaches, and ATP production was measured. FR30 drastically reduced placental and fetal weights. FR30 placentas displayed 14 proteins that were differentially expressed, including several mitochondrial proteins. FR30 induced a marked increase in placental mtDNA content and changes in mitochondrial functions, including modulation of the expression of genes implicated in biogenesis and bioenergetic pathways. FR30 mitochondria showed higher oxygen consumption but failed to maintain their ATP production. Maternal undernutrition induces placental mitochondrial abnormalities. Although an increase in biogenesis and bioenergetic efficiency was noted, placental ATP level was reduced. Our data suggest that placental mitochondrial defects may be implicated in fetoplacental pathologies.

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MATERNAL NUTRITION AND THE PROBLEM OF INTRAUTERINE DISEASE PROGRAMMING IN CHILDREN

Annals of the Russian academy of medical sciences ◽

10.15690/vramn988 ◽

2018 ◽

Vol 73 (3) ◽

pp. 190-194

Author(s):

O. P. Kovtun ◽

P. B. Tsyvian

Keyword(s):

Maternal Nutrition ◽

Metabolic Diseases ◽

Maternal Diet ◽

Experimental Studies ◽

Fetal Exposure ◽

Macronutrient Composition ◽

Maternal Environment ◽

Angiotensin System ◽

Maternal Undernutrition

Environmental conditions during perinatal development such as maternal undernutrition or overnutrition can program changes in the integration among physiological systems leading to cardio-metabolic diseases. This phenomenon can be understood in the context of the phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental input without genetic change. Experimental studies indicate that fetal exposure to an adverse maternal environment may alter the morphology and physiology that contribute to the development of cardio-metabolic diseases. The significance and role of genetic polymorphism, markers of chronic inflammation, oxidative stress, endothelial dysfunction, leptin synthesis disruption, rennin-angiotensin system in intrauterine cardio-metabolic disease programming are discussed. The study demonstrated that both maternal protein restriction and overnutrition alter the central and peripheral control of arterial pressure and metabolism. Breastfeeding may have beneficial effect on obesity risk later in life in genetically predisposed groups. Understanding the mechanisms which affect health outcomes in the offspring influenced by the macronutrient composition of the maternal diet during pregnancy or lactation may lead to new maternal nutrition recommendations, disease prevention strategies, and therapies that reduce the increasing incidence of cardio-metabolic diseases in children and adults.

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The influence of maternal protein nutrition on offspring development and metabolism: the role of glucocorticoids

Proceedings of The Nutrition Society ◽

10.1017/s0029665111003363 ◽

2011 ◽

Vol 71 (1) ◽

pp. 198-203 ◽

Cited By ~ 4

Author(s):

K. Almond ◽

P. Bikker ◽

M. Lomax ◽

M. E. Symonds ◽

A. Mostyn

Keyword(s):

Maternal Diet ◽

Protein Supplementation ◽

Maternal Environment ◽

Maternal Undernutrition ◽

Low Protein ◽

Increased Risk ◽

Neonatal Body Composition ◽

Tissue Sensitivity ◽

Protein Diets

The consequences of sub-optimal nutrition through alterations in the macronutrient content of the maternal diet will not simply be reflected in altered neonatal body composition and increased mortality, but are likely to continue into adulthood and confer greater risk of metabolic disease. One mechanism linking manipulations of the maternal environment to an increased risk of later disease is enhanced fetal exposure to glucocorticoids (GC). Tissue sensitivity to cortisol is regulated, in part, by the GC receptor and 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Several studies have shown the effects of maternal undernutrition, particularly low-protein diets, on the programming of GC action in the offspring; however, dietary excess is far more characteristic of the diets consumed by contemporary pregnant women. This study investigated the programming effects of moderate protein supplementation in pigs throughout pregnancy. We have demonstrated an up-regulation of genes involved in GC sensitivity, such as GC receptor and 11β-HSD, in the liver, but have yet to detect any other significant changes in these piglets, with no differences observed in body weight or composition. This increase in GC sensitivity was similar to the programming effects observed following maternal protein restriction or global undernutrition during pregnancy.

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Cinnamon Oil Inhibits Penicillium expansum Growth by Disturbing the Carbohydrate Metabolic Process

Journal of Fungi ◽

10.3390/jof7020123 ◽

2021 ◽

Vol 7 (2) ◽

pp. 123

Author(s):

Tongfei Lai ◽

Yangying Sun ◽

Yaoyao Liu ◽

Ran Li ◽

Yuanzhi Chen ◽

...

Keyword(s):

Pentose Phosphate ◽

Metabolic Process ◽

Penicillium Expansum ◽

Economic Losses ◽

Pome Fruit ◽

Cinnamon Oil ◽

Atp Production ◽

Protein Levels ◽

Regulatory Enzymes ◽

Expression Of Genes

Penicillium expansum is a major postharvest pathogen that mainly threatens the global pome fruit industry and causes great economic losses annually. In the present study, the antifungal effects and potential mechanism of cinnamon oil against P. expansum were investigated. Results indicated that 0.25 mg L−1 cinnamon oil could efficiently inhibit the spore germination, conidial production, mycelial accumulation, and expansion of P. expansum. In addition, it could effectively control blue mold rots induced by P. expansum in apples. Cinnamon oil could also reduce the expression of genes involved in patulin biosynthesis. Through a proteomic quantitative analysis, a total of 146 differentially expressed proteins (DEPs) involved in the carbohydrate metabolic process, most of which were down-regulated, were noticed for their large number and functional significance. Meanwhile, the expressions of 14 candidate genes corresponding to DEPs and the activities of six key regulatory enzymes (involving in cellulose hydrolyzation, Krebs circle, glycolysis, and pentose phosphate pathway) showed a similar trend in protein levels. In addition, extracellular carbohydrate consumption, intracellular carbohydrate accumulation, and ATP production of P. expansum under cinnamon oil stress were significantly decreased. Basing on the correlated and mutually authenticated results, we speculated that disturbing the fungal carbohydrate metabolic process would be partly responsible for the inhibitory effects of cinnamon oil on P. expansum growth. The findings would provide new insights into the antimicrobial mode of cinnamon oil.

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Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain

International Journal of Molecular Sciences ◽

10.3390/ijms22158325 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8325

Author(s):

Paola Zanfardino ◽

Stefano Doccini ◽

Filippo M. Santorelli ◽

Vittoria Petruzzella

Keyword(s):

Human Brain ◽

Basic Function ◽

Mitochondrial Proteome ◽

Novel Proteins ◽

Mitochondrial Functions ◽

Organ Specific ◽

Oxphos System ◽

Mitochondrial Defects ◽

Energy Dependent ◽

The Brain

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism, mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic origin of the OxPhos complexes is one of the reasons for the complexity of the genotype-phenotype correlation when facing human diseases associated with mitochondrial defects. Such complexity clinically manifests with extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the future directions of the multi-omics study of human brain disorders.

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The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

European Journal of Nutrition ◽

10.1007/s00394-021-02572-6 ◽

2021 ◽

Author(s):

Priscilla Day-Walsh ◽

Emad Shehata ◽

Shikha Saha ◽

George M. Savva ◽

Barbora Nemeckova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Human Colon ◽

Human Studies ◽

Bacterial Strains ◽

Increased Risk ◽

Carnitine Metabolism ◽

Registration Number ◽

Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

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Unusual increase of Scd1 and Elovl6 expression in rat inguinal adipose tissue

Open Life Sciences ◽

10.2478/s11535-012-0007-6 ◽

2012 ◽

Vol 7 (2) ◽

pp. 192-200

Author(s):

Jacek Turyn ◽

Adriana Mika ◽

Piotr Stepnowski ◽

Julian Swierczynski

Keyword(s):

Adipose Tissue ◽

Food Restriction ◽

Metabolic Diseases ◽

Quantitative Polymerase Chain Reaction ◽

Mrna Levels ◽

Gene Expressions ◽

Tissue Mass ◽

Expression Of Genes ◽

Fat Deposits ◽

Rat Adipose Tissue

AbstractIt is generally accepted that the location of body fat deposits may play an important role in the risk of developing some endocrine and metabolic diseases. We have studied the effect of food restriction and food restriction/refeeding, often practiced by individuals trying to lose body weight, on the expression of genes which are associated with obesity and certain metabolic disorders in inguinal, epididymal, and perirenal rat white adipose tissues. Gene expression was analyzed by real time semi-quantitative polymerase chain reaction and by Western blot. We found that prolonged food restriction caused a significant decrease of body and adipose tissue mass as well as the increase of Scd1 and Elovl6 gene expressions in all main rat adipose tissue deposits. Food restriction/refeeding caused increases of: a) Scd1 and Elovl6 mRNA levels in adipose tissue, b) Scd1 protein level and c) desaturation index in adipose tissue. The increased expression of both genes was unusually high in inguinal adipose tissue. The results suggest that the increase of Scd1 and Elovl6 gene expressions in white adipose tissue by prolonged food restriction and prolonged food restriction/refeeding may contribute to accelerated fat recovery that often occurs in individuals after food restriction/refeeding.

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Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

Oncogene ◽

10.1038/s41388-021-01886-3 ◽

2021 ◽

Author(s):

Rósula García-Navas ◽

Pilar Liceras-Boillos ◽

Carmela Gómez ◽

Fernando C. Baltanás ◽

Nuria Calzada ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Redox Homeostasis ◽

Atp Production ◽

Oxidative Energy Metabolism ◽

Ras Activation ◽

Mitochondrial Defects ◽

Critical Requirement ◽

Dynamics And Function ◽

And Function ◽

And Control

AbstractSOS1 ablation causes specific defective phenotypes in MEFs including increased levels of intracellular ROS. We showed that the mitochondria-targeted antioxidant MitoTEMPO restores normal endogenous ROS levels, suggesting predominant involvement of mitochondria in generation of this defective SOS1-dependent phenotype. The absence of SOS1 caused specific alterations of mitochondrial shape, mass, and dynamics accompanied by higher percentage of dysfunctional mitochondria and lower rates of electron transport in comparison to WT or SOS2-KO counterparts. SOS1-deficient MEFs also exhibited specific alterations of respiratory complexes and their assembly into mitochondrial supercomplexes and consistently reduced rates of respiration, glycolysis, and ATP production, together with distinctive patterns of substrate preference for oxidative energy metabolism and dependence on glucose for survival. RASless cells showed defective respiratory/metabolic phenotypes reminiscent of those of SOS1-deficient MEFs, suggesting that the mitochondrial defects of these cells are mechanistically linked to the absence of SOS1-GEF activity on cellular RAS targets. Our observations provide a direct mechanistic link between SOS1 and control of cellular oxidative stress and suggest that SOS1-mediated RAS activation is required for correct mitochondrial dynamics and function.

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Offspring’s hydromineral adaptive responses to maternal undernutrition during lactation

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017441500135x ◽

2015 ◽

Vol 6 (6) ◽

pp. 520-529 ◽

Cited By ~ 3

Author(s):

P. Nuñez ◽

J. Arguelles ◽

C. Perillan

Keyword(s):

Salt Intake ◽

Maternal Diet ◽

Plasma Osmolality ◽

Control Mechanisms ◽

Lactation Period ◽

Adaptive Responses ◽

Long Term Effects ◽

Molecular Alterations ◽

Maternal Undernutrition ◽

Renal Histology

Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams’ restriction.

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Mechanisms involved in developmental programming of hypertension and renal diseases. Gender differences

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0054 ◽

2014 ◽

Vol 18 (2) ◽

Cited By ~ 6

Author(s):

Analia Lorena Tomat ◽

Francisco Javier Salazar

Keyword(s):

Metabolic Diseases ◽

Current Knowledge ◽

Adult Life ◽

Developmental Programming ◽

Renal Diseases ◽

Future Studies ◽

Functional Changes ◽

Regulatory Systems ◽

Increased Risk ◽

Renal Changes

AbstractA substantial body of epidemiological and experimental evidence suggests that a poor fetal and neonatal environment may “program” susceptibility in the offspring to later development of cardiovascular, renal and metabolic diseases.This review focuses on current knowledge from the available literature regarding the mechanisms linking an adverse developmental environment with an increased risk for cardiovascular, renal and metabolic diseases in adult life. Moreover, this review highlights important sex-dependent differences in the adaptation to developmental insults.Developmental programming of several diseases is secondary to changes in different mechanisms inducing important alterations in the normal development of several organs that lead to significant changes in birth weight. The different diseases occurring as a consequence of an adverse environment during development are secondary to morphological and functional cardiovascular and renal changes, to epigenetic changes and to an activation of several hormonal and regulatory systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived metabolites, oxidative stress and inflammation. The important sex-dependent differences in the developmental programming of diseases seem to be partly secondary to the effects of sex hormones. Recent studies have shown that the progression of these diseases is accelerated during aging in both sexes.The cardiovascular, renal and metabolic diseases during adult life that occur as a consequence of several insults during fetal and postnatal periods are secondary to multiple structural and functional changes. Future studies are needed in order to prevent the origin and reduce the incidence and consequences of developmental programmed diseases.

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Adipose tissue: from amorphous filler to metabolic mastermind

The Biochemist ◽

10.1042/bio_2021_113 ◽

2021 ◽

Author(s):

Silvia Corvera

Keyword(s):

Adipose Tissue ◽

Metabolic Diseases ◽

Disease Risk ◽

Appetite Control ◽

Fat Storage ◽

Fuel Distribution ◽

Adipose Tissue Depots ◽

Increased Risk ◽

Adipocyte Hypertrophy ◽

Adipocyte Hyperplasia

Adipose tissue plays a central role in the control of systemic glucose homeostasis through two major mechanisms: fat storage and secretion of specific cytokines known as adipokines. Fat storage in adipose tissue is critically important, as it prevents lipid deposition in liver and muscle, which in turn results in insulin resistance and increased risk of type 2 diabetes. Secretion of adipokines, such as leptin, protects from fuel depletion through appetite control, and other adipokines control fuel distribution and utilization. Fat storage capacity of adipose tissue increases through two mechanisms, adipocyte hypertrophy and adipocyte hyperplasia. Adipose tissue depots expand differently in diverse individuals and confer varying degrees of metabolic disease risk. There are multiple adipocyte subtypes that together mediate the functions of adipose tissue. They do so through specialized functions such as thermogenesis, which burns fuel to maintain core temperature, and through selective secretion of different adipokines. Much progress has been made in understanding the mechanisms by which adipose tissue controls systemic metabolism, increasing our hope of developing new, effective therapies for metabolic diseases.

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