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The aim of this study was to examine the effect of three different fatty acid (FA)-rich meals enriched in either saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) on postprandial metabolic responses in premenopausal, normal weight women. For this randomized, single-blind, crossover study three high-fat (HF) meals rich in either SFA, MUFA, or PUFA (65% energy from fat; 35% of participants’ total daily energy needs) were tested. For each visit, anthropometrics and resting metabolic rate were measured following a 12-15h fast. Then, participants consumed one of the HF meals and respiratory gases were collected using indirect calorimetry for 3h postprandially. Energy expenditure (EE) following a SFA-rich meal was a significantly higher than a MUFA-rich meal (p=0.04; η2 = .19) but SFA was not significantly different from PUFA. There was a trend towards significance in EE between PUFA and MUFA (p=0.06). After adjusting for fat-free mass (FFM), there were no longer condition or time effects for EE, although FFM remained a significant predictor (p=0.005; η2=.45). There were no significant differences between conditions for dietary induced thermogenesis (DIT) or substrate oxidation. A relationship between fat-mass (FM) and both total fat oxidation (r=.62; p=0.025) and total change in respiratory exchange ratio following a MUFA-rich meal, was observed (r=-.55; p=0.05). In conclusion, weight loss through increases in EE may be best achieved by increasing FFM rather than selection of FA type. Further, a relationship exists between FM and fat oxidation following a MUFA-rich meal, most likely due to an unidentified mechanism.
Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.
The development and maintenance of body composition and functions require an adequate protein intake with a continuous supply of amino acids (AA) to tissues. Body pool and AA cellular concentrations are tightly controlled and maintained through AA supply (dietary intake, recycled from proteolysis and de novo synthesis), AA disposal (protein synthesis and other AA-derived molecules) and AA losses (deamination and oxidation). Different molecular regulatory pathways are involved in the control of AA sufficiency including the mechanistic target of rapamycin complex 1, the general control non-derepressible 2/activating transcription factor 4 system or the fibroblast growth factor 21. There is a tight control of protein intake, and human subjects and animals appear capable of detecting and adapting food and protein intake and metabolism in face of foods or diets with different protein contents. A severely protein deficient diet induces lean body mass losses and ingestion of sufficient dietary energy and protein is a prerequisite for body protein synthesis and maintenance of muscle, bone and other lean tissues and functions. Maintaining adequate protein intake with age may help preserve muscle mass and strength but there is an ongoing debate as to the optimal protein intake in older adults. The protein synthesis response to protein intake can also be enhanced by prior completion of resistance exercise but this effect could be somewhat reduced in older compared to young individuals and gain in muscle mass and function due to exercise require regular training over an extended period.
Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8–20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.
Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.
The quantification of physiological and immunological functions provides fundamental information on individual state. It fosters our understanding of the costs of and constraints on life-history strategies. Research in this area on kestrels has mainly focused on immunity, energetics, hormones and antioxidants. This chapter discusses the factors that impact the immune function and describes a number of parasites and pathogens that can be detected in kestrels. It shows how the different phases of reproduction face males and females with different energetic and physiological demands. It discusses the costs associated with sibling competition, and how male and female nestlings may differ in how they optimise the trade-off between growth and self-maintenance. Finally, this chapter describes the moult phase, which represents an understudied feature of kestrel biology.
Selection for prolificacy in sows has resulted in higher metabolic demands during lactation. In addition, modern sows have an increased genetic merit for leanness. Consequently, sow metabolism during lactation has changed, possibly affecting milk production and litter weight gain. The aim of this study was to investigate the effect of lactational feed intake on milk production and relations between mobilization of body tissues (adipose tissue or skeletal muscle) and milk production in modern sows with a different lactational feed intake. A total of 36 primiparous sows were used, which were either full-fed (6.5 kg/day) or restricted-fed (3.25 kg/day) during the last 2 weeks of a 24-day lactation. Restricted-fed sows had a lower milk fat percentage at weaning and a lower litter weight gain and estimated milk fat and protein production in the last week of lactation. Next, several relations between sow body condition (loss) and milk production variables were identified. Sow BW, loin muscle depth and backfat depth at parturition were positively related to milk fat production in the last week of lactation. In addition, milk fat production was related to the backfat depth loss while milk protein production was related to the loin muscle depth loss during lactation. Backfat depth and loin muscle depth at parturition were positively related to lactational backfat depth loss or muscle depth loss, respectively. Together, results suggest that sows which have more available resources during lactation, either from a higher amount of body tissues at parturition or from an increased feed intake during lactation, direct more energy toward milk production to support a higher litter weight gain. In addition, results show that the type of milk nutrients that sows produce (i.e. milk fat or milk protein) is highly related to the type of body tissues that are mobilized during lactation. Interestingly, relations between sow body condition and milk production were all independent of feed level during lactation. Sow management strategies to increase milk production and litter growth in modern sows may focus on improving sow body condition at the start of lactation or increasing feed intake during lactation.
The dicamba-resistant cropping system was developed to be used as a tool to control multiple-resistant weed species, particularly Palmer amaranth (Amaranthus palmeri S. Watson). However, dicamba applications have resulted in off-target movement of the herbicide to susceptible neighboring vegetation, with frequent damage to non–dicamba resistant soybean [Glycine max (L.) Merr.]. Pod malformation and subsequent auxin-like injury to progeny is common when parent soybean plants are exposed to the herbicide post-flowering. Yet no publication to date has conveyed the presence of dicamba in seed. The objective of this study was to determine whether dicamba exists and at what quantities inside soybean seed following a low-dose exposure in the pod-filling stage using radiolabeled herbicide as a tracer. Non–dicamba resistant soybean plants were grown in the greenhouse until the pod-filling growth stage and then treated with 2.8 g ae ha−1 of dicamba (1/200 of the recommended rate of 560 g ae ha−1). Immediately afterward, [14C]dicamba (approximately 6.4 kBq per plant) was applied to the adaxial surface of one trifoliate leaf located in the midportion of each plant. The greatest amount of [14C]dicamba recovered was in seeds and in pods, and these plant parts accumulated 44% and 38% of the total absorbed, respectively. Chromatography results showed that the totality of the [14C]dicamba present in the soybean seeds was in the phytotoxic form, except for a single sample, in which one metabolite was detected (possibly 5-hydroxy dicamba). Precautions should be taken to avoid dicamba exposure to sensitive soybean fields, especially those dedicated to seed production, as this may result in low seed quality and symptomology on progeny plants.
Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients.
We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients.
Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006.
Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology.
Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.
There is an urgent need to find alternative feed resources that can further substitute fishmeal in Atlantic salmon diets without compromising health and food quality, in particular during the finishing feeding period when the feed demand is highest and flesh quality effects are most significant. This study investigates efficacy of substituting a isoprotein (35 %) and isolipid (35 %) low fishmeal diet (FM, 15 %) with Antarctic krill meal (KM, 12 %) during 3 months with growing finishing 2·3 kg salmon (quadruplicate sea cages/diet). Final body weight (3·9 (se 0·04) kg) was similar in the dietary groups, but the KM group had more voluminous body shape, leaner hearts and improved fillet integrity, firmness and colour. Ectopic epithelial cells and focal Ca deposits in intestine were only detected in the FM group. Transcriptome profiling by microarray of livers showed dietary effects on several immune genes, and a panel of structural genes were up-regulated in the KM group, including cadherin and connexin. Up-regulation of genes encoding myosin heavy chain proteins was the main finding in skeletal muscle. Morphology examination by scanning electron microscopy and secondary structure by Fourier transform IR spectroscopy revealed more ordered and stable collagen architecture of the KM group. NEFA composition of skeletal muscle indicated altered metabolism of n-3, n-6 and SFA of the KM group. The results demonstrated that improved health and meat quality in Atlantic salmon fed krill meal were associated with up-regulation of immune genes, proteins defining muscle properties and genes involved in cell contacts and adhesion, altered fatty acid metabolism and fat deposition, and improved gut health and collagen structure.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.
The objective was to elucidate the effects of dietary supplementation with guanidinoacetic acid (GAA) on performance, egg quality and the liver antioxidant activity of laying hens. A total of 128, 72-week-old ISA Brown laying hens were randomly divided into four equal groups (32 birds), and each subgroup had eight replicates (four birds/cage). The control group (GAA0) fed the basal diet with no supplements, while the other experimental groups fed the basal diets supplemented with 0.5 (GAA1), 1.0 (GAA2) and 1.5 (GAA3) g of GAA/kg diet. The experiment lasted for 6 weeks. The addition of GAA at a rate of 1.5 g kg−1 significantly increased the hen-day egg production and egg mass as compared to the control group (P = 0.016 and 0.003, respectively). Although the egg weight was not affected (P = 0.521) by the dietary supplements, the shell ratio, shell thickness, yolk index and Haugh units increased linearly with the increase in the dietary supplements of the GAA (P = 0.036, 0.001, 0.012 and 0.004, respectively). The liver MDA levels decreased linearly with the increment in the dietary levels of the GAA (P = 0.012). Birds in the GAA2 and GAA3 showed a significantly higher liver nitric oxide level (52.50 and 54.21 mg/g, respectively) when compared with GAA0 and GAA1 groups (P = 0.029). Compared to the GAA0 group, all GAA-supplemented groups showed significantly higher liver ATP levels (P = 0.047). In conclusion, the dietary GA supplements at doses of 1.0 or 1.5 g kg−1 may improve the laying performance, antioxidant activity and the status of cellular energy metabolism in laying hens.
Host-associated microbiomes are ubiquitous in nature, but highly variable in both space and time, and shaped by a diverse range of biotic and abiotic factors. This chapter summarises the numerous drivers of variation in microbiome structure and function across both plants and animals. Plants harbour distinct microbial communities in their rhizosphere, phyllosphere and endosphere. These communities interact with hosts in a different way, and in turn are shaped by a unique set of environmental factors. For example, the rhizosphere supports a particularly diverse microbial community shaped by plant exudates and signalling molecules to facilitate nutrient transfer to the host. Similarly, variation in animal microbiomes is driven by host genetic, life-history and environmental traits, including phylogeny, diet, age, metabolism and sociality. Several of these factors are also given more detailed treatment in later chapters. Particular attention is given to our current state of knowledge concerning initial colonisation and subsequent succession in microbial community composition in juveniles, the consequences of which remain one of the major outstanding questions in microbiome research.
Coordinated changes in energy metabolism develop to support gestation and lactation in the periparturient dairy cow. Maternal physiology involves the partitioning of nutrients (i.e. glucose, amino acids and fatty acids (FA)) for fetal growth and milk synthesis. However, the inability of the dairy cow to successfully adapt to a productive lactation may trigger metabolic stress characterized by uncontrolled adipose tissue lipolysis and reduced insulin sensitivity. A consequence is lipotoxicity and hepatic triglyceride deposition that favors the development of fatty liver disease (FLD) and ketosis. This review describes contemporary perspectives pertaining to FA surfeit and complex lipid metabolism in the transition dairy cow. The role of saturated and unsaturated FA as bioactive signaling molecules capable of modulating insulin secretion and sensitivity is explored. Moreover, the metabolic fate of FA as influenced by mitochondrial function is considered. This includes the influence of inadequate mitochondrial oxidation on acylcarnitine status and the use of FA for lipid mediator synthesis. Lipid mediators, including the sphingolipid ceramide and diacylglycerol, are evaluated considering their established ability to inhibit insulin signaling and glucose transport in non-ruminant diabetics. The mechanisms of FLD in the transition cow are revisited with attention centered on glycerophospholipid phosphatidylcholine and triglyceride secretion. The relationship between oxidative stress and oxylipids within the context of insulin antagonism, hepatic steatosis and inflammation is also reviewed. Lastly, peripartal hormonal involvement or lack thereof of adipokines (i.e. leptin, adiponectin) and hepatokines (i.e. fibroblast growth factor-21) is described. Similarities and differences in ruminant and non-ruminant physiology are routinely showcased. Unraveling the lipidome of the dairy cow has generated breakthroughs in our understanding of periparturient lipid biology. Therapeutic approaches that target FA and complex lipid metabolism holds promise to enhance cow health, well-being and productive lifespan.
Inflammatory cascades are a critical component of the immune response to infection or tissue damage, involving an array of signals, including water-soluble metabolites, lipid mediators and several classes of proteins. Early investigation of these signaling pathways focused largely on immune cells and acute disease models. However, more recent findings have highlighted critical roles of both immune cells and inflammatory mediators on tissue remodeling and metabolic homeostasis in healthy animals. In dairy cattle, inflammatory signals in various tissues and in circulation change rapidly and dramatically, starting just prior to and at the onset of lactation. Furthermore, several observations in healthy cows point to homeostatic control of inflammatory tone, which we define as a regulatory process to balance immune tolerance with activation to keep downstream effects under control. Recent evidence suggests that peripartum inflammatory changes influence whole-body nutrient flux of dairy cows over the course of days and months. Inflammatory mediators can suppress appetite, even at levels that do not induce acute responses (e.g. fever), thereby decreasing nutrient availability. On the other hand, inhibition of inflammatory signaling with non-steroidal anti-inflammatory drug (NSAID) treatment suppresses hepatic gluconeogenesis, leading to hypoglycemia in some cases. Over the long term, though, peripartum NSAID treatment substantially increases peak and whole-lactation milk synthesis by multiparous cows. Inflammatory regulation of nutrient flux may provide a homeorhetic mechanism to aid cows in adapting to rapid changes in metabolic demand at the onset of lactation, but excessive systemic inflammation has negative effects on metabolic homeostasis through inhibition of appetite and promotion of immune cell activity. Thus, in this review, we provide perspectives on the overlapping regulation of immune responses and metabolism by inflammatory mediators, which may provide a mechanistic underpinning for links between infectious and metabolic diseases in transition dairy cows. Moreover, we point to novel approaches to the management of this challenging phase of the production cycle.
Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of retinal illumination on photoreceptor metabolism, effects of light modulation on the severity of diabetic retinopathy, and recent clinical trials testing the treatment of diabetic retinopathy with interventions that impact photoreceptor metabolism. Finally, we introduce several possible mechanisms that could link photoreceptor responses to light and the development of retinal vascular disease in diabetes. Collectively, these concepts form the basis for a growing body of investigative efforts aimed at developing novel pharmacologic and nonpharmacologic tools that target photoreceptor physiology to treat a very common cause of blindness across the world.
Darwin's theory of evolution emphasized that positive selection of functional proficiency provides the fitness that ultimately determines the structure of life, a view that has dominated biochemical thinking of enzymes as perfectly optimized for their specific functions. The 20th-century modern synthesis, structural biology, and the central dogma explained the machinery of evolution, and nearly neutral theory explained how selection competes with random fixation dynamics that produce molecular clocks essential e.g. for dating evolutionary histories. However, quantitative proteomics revealed that selection pressures not relating to optimal function play much larger roles than previously thought, acting perhaps most importantly via protein expression levels. This paper first summarizes recent progress in the 21st century toward recovering this universal selection pressure. Then, the paper argues that proteome cost minimization is the dominant, underlying ‘non-function’ selection pressure controlling most of the evolution of already functionally adapted living systems. A theory of proteome cost minimization is described and argued to have consequences for understanding evolutionary trade-offs, aging, cancer, and neurodegenerative protein-misfolding diseases.
Metabolically healthy obesity refers to a subset of obese people with a normal metabolic profile. We aimed to explore the association between metabolically healthy and obesity status and risk of hypertension among Chinese adults from The Rural Chinese Cohort Study. This prospective cohort study enrolled 9137 Chinese adults without hypertension, type 2 diabetes or treatment for lipid abnormality at baseline (2007–2008) and followed up during 2013–2014. Modified Poisson regression models were used to examine the risk of hypertension by different metabolically healthy and obesity status, estimating relative risks (RR) and 95 % CI. During 6 years of follow-up, we identified 1734 new hypertension cases (721 men). After adjusting for age, sex, smoking and other confounding factors, risk of hypertension was increased with metabolically healthy general obesity (MHGO) defined by BMI (RR 1·75, 95 % CI 1·02, 3·00) and metabolically healthy abdominal obesity (MHAO) defined by waist circumference (RR 1·51, 95 % CI 1·12, 2·04) as compared with metabolically healthy non-obesity. The associations between metabolically healthy and obesity status and hypertension outcome were consistent after stratifying by sex, age, smoking, alcohol drinking and physical activity. Both MHGO and MHAO were associated with increased risk of hypertension. Obesity control programmes should be implemented to prevent or delay the development of hypertension in rural China.
Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.
Weaning is known to induce important nutritional and energetic stress in piglets. Low-birthweight (LBW) piglets, now frequently observed in swine production, are more likely to be affected. The weaning period is also associated with dysfunctional immune responses, uncontrolled inflammation and oxidative stress conditions that are recognized risk factors for infections and diseases. Mounting evidence indicates that mitochondria, the main cellular sources of energy in the form of adenosine 5′ triphosphate (ATP) and primary sites of reactive oxygen species production, are related to immunity, inflammation and bacterial pathogenesis. However, no information is currently available regarding the link between mitochondrial energy production and oxidative stress in weaned piglets. The objective of this study was to characterize markers of cellular and mitochondrial energy metabolism and oxidative status in both normal-birthweight (NBW) and LBW piglets throughout the peri-weaning period. To conduct the study, 30 multiparous sows were inseminated and litters were standardized to 12 piglets. All the piglets were weighted at day 1 and 120 piglets were selected and assigned to 1 of 2 experimental groups: NBW (n = 60, mean weight of 1.73 ± 0.01 kg) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect plasma and organ (liver, intestine and kidney) samples. Analysis revealed that ATP concentrations were lower in liver of piglets after weaning than during lactation (P < 0.05) thus suggesting a significant impact of weaning stress on mitochondrial energy production. Oxidative damage to DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and proteins (carbonyls) measured in plasma increased after weaning and this coincides with a rise in enzymatic antioxidant activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) (P < 0.05). Mitochondrial activities of both GPx and SOD are also significantly higher (P < 0.05) in kidney of piglets after weaning. Additionally, oxidative damage to macromolecules is more important in LBW piglets as measured concentrations of 8-OHdG and protein carbonyls are significantly higher (P < 0.05) in plasma and liver samples, respectively, than for NBW piglets. These results provide novel information about the nature, intensity and duration of weaning stress by revealing that weaning induces mitochondrial dysfunction and cellular oxidative stress conditions which last for at least 2 weeks and more severely impact smaller piglets.