Maternal high fat-high energy diet alters metabolic factors in the non-human primate fetal heart.

The consumption of high fat-high energy diets (HF-HEDs) continues to rise worldwide and parallels the rise in maternal obesity (MO) that predisposes offspring to cardiometabolic disorders. Although the underlying mechanisms are unclear, thyroid hormones (TH) modulate cardiac maturation in utero. Therefore, we aimed to determine the impact of a high fat-high energy diet (HF-HED) on the hormonal, metabolic and contractility profile of the non-human primate (NHP) fetal heart. At ∼9 months preconception, female baboons (Papio hamadryas) were randomly assigned to either a control diet or HF-HED. At 165 days gestational age (term = 184 days), fetuses were delivered by Caesarean section under anaesthesia, humanely killed, and left ventricular cardiac tissue (Control (n = 6 female, 6 male); HF-HED (n = 6 F, 6 M)) was collected. Maternal HF-HED decreased the concentration of active cardiac TH (i.e. triiodothyronine (T3)), and type 1 iodothyronine deiodinase (DIO1) mRNA expression. Maternal HF-HED decreased the abundance of cardiac markers of insulin-mediated glucose uptake phosphorylated insulin receptor substrate 1 (Ser789) and glucose transporter 4, and increased protein abundance of key oxidative phosphorylation complexes (I, III, IV) and mitochondrial abundance in both sexes. Maternal HF-HED alters cardiac TH status, which may induce early signs of cardiac insulin resistance. This may increase the risk of cardiometabolic disorders in later life in offspring born to these pregnancies. KEY POINTS: Babies born to mothers who consume a high fat-high energy diet (HF-HED) prior to and during pregnancy are predisposed to an increased risk of cardiometabolic disorders across the life course. Maternal HF-HED prior to and during pregnancy decreased thyroid hormone triiodothyronine (T3) concentrations and type 1 iodothyronine deiodinase DIO1 mRNA expression in the non-human primate fetal heart. Maternal HF-HED decreased markers of insulin-dependent glucose uptake, phosphorylated insulin receptor substrate 1 and glucose transporter 4 in the fetal heart. Maternal HF-HED increased mitochondrial abundance and mitochondrial OXPHOS complex I, III and IV in the fetal heart. Fetuses from HF-HED pregnancies are predisposed to cardiometabolic disorders that may be mediated by changes in T3, placing them on a poor lifetime cardiovascular health trajectory.

Comparing effects of high starch diet or high lipid diet supplemented with different levels of zinc on intestinal barrier and microbe community in largemouth bass Micropterus salmoides.

Zinc is essential for normal growth and reproduction in all animals and plays a crucial role in many biological processes. The present study aimed to compare the intervention effects of zinc on intestinal health in a high lipid diet or high starch diet. Seven iso-nitrogenous (∼520 g kg-1) diets were formulated containing a positive control diet (115 g kg-1 lipid + 115 g kg-1 starch + 20 mg kg-1 Zn), three high starch diets (HS, 166 g kg-1 starch) and three high lipid diets (HL, 182 g kg-1 lipid), with 0 (HS-LZn, HL-LZn), 20 (HS-MZn, HL-MZn) and 150 (HS-HZn, HL-HZn) mg kg-1 Zn being supplemented. High starch diet and high lipid diet promoted feed efficiency, as evidenced by the lower feed conversion ratio. Three-way factorial ANOVA analysis showed high starch diet (166 g kg-1) significantly decreased final body weight and weight gain compared to the normal starch level (115 g kg-1). Diamine oxidase in serum significantly increased in diets HS-LZn and HL-LZn. In addition, distal intestinal mucosal fold damage and inflammatory infiltration were observed in the HS-LZn, HS-HZn, HL-LZn and HL-HZn groups. Fish fed HL diets (HL-LZn, HL-MZn, HL-HZn) showed lower expressions of claudin 5 and claudin 34, and higher IgD and IgM. Diets HL-LZn and HL-MZn significantly up-regulated C4 and C7. Proinflammatory cytokines including il8, il1ß and tnfα significantly up-regulated in diet HL-LZn, even higher than the HS-LZn. Intestinal microbial composition indicated the abundance of Cetobacterium in HL-LZn was significantly higher than the control and HL-MZn diets. Similarly, LEfSe showed that Cetobacterium (P = 0.039) significantly enriched in the HL-LZn group. This study clarified high energy diet induced intestinal damage, which can be alleviated by zinc.

Characterization of A-to-I Editing in Pigs under a Long-Term High-Energy Diet.

Long-term high-energy intake has detrimental effects on pig health and elevates the risk of metabolic disease. RNA editing modifying RNA bases in a post-transcriptional process has been extensively studied for model animals. However, less evidence is available that RNA editing plays a role in the development of metabolic disorders. Here, we profiled the A-to-I editing in three tissues and six gut segments and characterized the functional aspect of editing sites in model pigs for metabolic disorders. We detected 64,367 non-redundant A-to-I editing sites across the pig genome, and 20.1% correlated with their located genes' expression. The largest number of A-to-I sites was found in the abdominal aorta with the highest editing levels. The significant difference in editing levels between high-energy induced and control pigs was detected in the abdominal aorta, testis, duodenum, ileum, colon, and cecum. We next focused on 6041 functional A-to-I sites that detected differences or specificity between treatments. We found functional A-to-I sites specifically involved in a tissue-specific manner. Two of them, located in gene SLA-DQB1 and near gene B4GALT5 were found to be shared by three tissues and six gut segments. Although we did not find them enriched in each of the gene features, in correlation analysis, we noticed that functional A-to-I sites were significantly enriched in gene 3'-UTRs. This result indicates, in general, A-to-I editing has the largest potential in the regulation of gene expression through changing the 3'-UTRs' sequence, which is functionally involved in pigs under a long-term high-energy diet. Our work provides valuable knowledge of A-to-I editing sites functionally involved in the development of the metabolic disorder.

Early unhealthy eating habits underlie morpho-functional changes in the liver and adipose tissue in male rats.

Early-life consumption of high-fat and sugar-rich foods is recognized as a major contributor for the onset of metabolic dysfunction and its related disorders, including diabetes and nonalcoholic fatty liver disease. The lifelong impact of early unhealthy eating habits that start at younger ages remains unclear. Therefore, to better understand the effects of diet, it is essential to evaluate the structural and functional changes induced in metabolic organs and potential mechanisms underlying those changes. To investigate the long-term effects of eating habits, young male rats were exposed to high-sugar and high-energy diets. After 14 weeks, body composition was assessed, and histopathological changes were analyzed in the liver and adipose tissue. Serum biochemical parameters were also determined. Expression of inflammatory markers in the liver was evaluated by immunohistochemistry. Our results revealed that serum levels of glucose, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile were increased in rats red high-sugar and high-energy diets. Histopathological alterations were observed, including abnormal hepatocyte organization and lipid droplet accumulation in the liver, and abnormal structure of adipocytes. In both unhealthy diet groups, hepatic expression of Toll-like receptor 4 (TLR4), cyclooxygenase 2 (COX-2), and E-selectin were increased, as well as a biomarker of oxidative stress. Together, our data demonstrated that unhealthy diets induced functional and structural changes in the metabolic organs, suggesting that proinflammatory and oxidative stress mechanisms trigger the hepatic alterations and metabolic dysfunction.

Maternal High-Energy Diet during Pregnancy and Lactation Impairs Neurogenesis and Alters the Behavior of Adult Offspring in a Phenotype-Dependent Manner.

Obesity is one of the biggest and most costly health challenges the modern world encounters. Substantial evidence suggests that the risk of metabolic syndrome or obesity formation may be affected at a very early stage of development, in particular through fetal and/or neonatal overfeeding. Outcomes from epidemiological studies indicate that maternal nutrition during pregnancy and lactation has a profound impact on adult neurogenesis in the offspring. In the present study, an intergenerational dietary model employing overfeeding of experimental mice during prenatal and early postnatal development was applied to acquire mice with various body conditions. We investigated the impact of the maternal high-energy diet during pregnancy and lactation on adult neurogenesis in the olfactory neurogenic region involving the subventricular zone (SVZ) and the rostral migratory stream (RMS) and some behavioral tasks including memory, anxiety and nociception. Our findings show that a maternal high-energy diet administered during pregnancy and lactation modifies proliferation and differentiation, and induced degeneration of cells in the SVZ/RMS of offspring, but only in mice where extreme phenotype, such as significant overweight/adiposity or obesity is manifested. Thereafter, a maternal high-energy diet enhances anxiety-related behavior in offspring regardless of its body condition and impairs learning and memory in offspring with an extreme phenotype.

Spirulina supplementation improves lipid metabolism and autophagic activities in the liver and muscle of Hu lambs fed a high-energy diet.

The current study aimed to examine the effects of dietary spirulina supplementation in high-energy (HE) diets on fatty acid metabolism in sheep, and preliminarily explored the potential mechanisms underlying the associated autophagy-mediated regulation of lipid metabolism. In a 2 × 3 factorial design, including six treatment combinations of two metabolisable energy diets (10 and 11 MJ/kg DM), three spirulina supplementation levels (0, 1%, and 3%) were used. Serum alanineaminotransferase (ALT) (p = 0.003) and aspartatetransaminase (AST) (p = 0.002) activities increased, whereas total PUFA content (p < 0.001) decreased in the liver of lambs fed a HE diet. With the addition of spirulina, serum ALT (p = 0.037) and AST (p = 0.014) activities decreased, whereas EPA (p = 0.004), GLA (p = 0.019), n-6 PUFA (p = 0.005), and total PUFA contents (p = 0.019) increased. Moreover, the crude protein content in the Longissimus thoracis et lumborum (LTL) increased (p = 0.013), the expression of PPARα and PPARγ was up-regulated, while ELOVL2 was down-regulated in liver and LTL (p < 0.05). Spirulina supplementation increased mRNA expression levels of autophagy-associated genes, including that of Beclin-1, AMPK, and ULK1 (p < 0.05). In conclusion, spirulina supplementation in a HE diet exerted a protective effect on the liver, increased PUFA content, and modulated expression levels of autophagy-related genes in growing lambs.

Effect of maternal obesity on fetal and postnatal baboon (Papio species) early life phenotype.

BACKGROUND: Non-human primate models of developmental programming by maternal obesity (MO) are needed for translation to human programming outcomes. We present baboon offspring (F1) morphometry, blood cortisol, and adrenocorticotropic hormone (ACTH) from 0.9 gestation to 0-2 years. METHODS: Control mothers ate chow; MO mothers ate high-fat high-energy diet pre-pregnancy through lactation. RESULTS: Maternal obesity mothers weighed more than controls pre-pregnancy. Maternal obesity gestational weight gain was lower with no correlation with fetal or placenta weights. At 0.9 gestation, MO and control F1 morphometry and ACTH were similar. MO-F1 0.9 gestation male cortisol was lower, rising slower from 0-2 years vs control-F1. At birth, male MO-F1 and control-F1 weights were similar, but growth from 0-2 years was steeper in MO-F1; newborn female MO-F1 weighed more than control-F1 but growth from 0-2 years was similar. ACTH did not change in either sex. CONCLUSIONS: Maternal obesity produced sexually dimorphic fetal and postnatal growth and hormonal phenotypes.

A predictive model of rat calorie intake as a function of diet energy density.

Easy access to high-energy food has been linked to high rates of obesity in the world. Understanding the way that access to palatable (high fat or high calorie) food can lead to overconsumption is essential for both preventing and treating obesity. Although the body of studies focused on the effects of high-energy diets is growing, our understanding of how different factors contribute to food choices is not complete. In this study, we present a mathematical model that can predict rat calorie intake to a high-energy diet based on their ingestive behavior to a standard chow diet. Specifically, we propose an equation that describes the relation between the body weight ( W), energy density ( E), time elapsed from the start of diet ( T), and daily calorie intake ( C). We tested our model on two independent data sets. Our results show that the suggested model can predict the calorie intake patterns with high accuracy. Additionally, the only free parameter of our proposed equation (ρ), which is unique to each animal, has a strong correlation with their calorie intake.

Isoquinoline alkaloids supplementation on performance and carcass traits of feedlot bulls.

OBJECTIVE: Isoquinoline Alkaloids, derived from one plant (Macleaya cordata) can be an alternative when it is desired to increase performance in feedlot cattle. However, results on these nutritional additives in high energy diets in ruminants are still incipient in literature. In this context, the objective of this study was to evaluate performance and carcass traits of feedlot bulls supplemented with sanguinarine, the main alkaloid presents in Macleaya cordata in high energy density diets. METHODS: Thirty-two crossbred Angus-Nelore bulls with mean initial body weight of 365±10 kg and mean initial age of 11±3 months were used. The experiment lasted 119 days, with 14 days of adaptation and 105 experimental days. Experimental diet consisted of 85% whole corn grains and 15% protein-vitamin-mineral nucleus and supplied ad libitum. Treatments consisted of a control diet (CON) and a diet with sanguinarine supplementation (SAN) at a dosage of 4 g of product sufficient to provide 6 mg of sanguinarine/d. Experimental design was completely randomized. RESULTS: Dry matter intake, average daily gain and feed conversion were similar (p>0.05) between treatments. However, SAN group animals had higher carcass yield (p = 0.045) and were more efficient in the transformation of dry matter consumed in carcass gain (p = 0.046) than CON. In addition, haptoglobin, increased throughout feedlot duration meaning high challenge for the animals due to the diet, but this behavior was similar (p>0.05) between treatments. CONCLUSION: Sanguinarine produced positive results in relation to carcass yield and could be used as an additive for bulls fed diets receiving high energy density diet.

Beneficial effects of cocoa, coffee, green tea, and garcinia complex supplement on diet induced obesity in rats.

BACKGROUND: Cocoa, coffee, green tea and garcinia contain large amounts of polyphenols. Polyphenols are well-known phytochemicals and found in plants, and have modulated physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. METHODS: To evaluate the obesity-lowering effect of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) in high-energy diet (HED)-induced obese rats. Male Sprague Dawley rats (8 weeks old) were randomly divided into four groups (n = 12 per group): normal diet with vehicle treatment (Control), and HED to receive vehicle or CCGG by oral gavage at 129, 258, or 517 mg/kg/day for 4 weeks, designated the HED, 0.5X, 1X and 1X groups, respectively. RESULTS: HED induced macrovesicular fat in the liver and the formation of adipose tissues, and significantly increased the levels of serum free fatty acids (FFA), triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ketone bodies in serum, and hepatic TG and TC levels, and decreased the levels of high density lipoprotein cholesterol (HDL-C) in serum and lipase activity in fat tissues. Treatment with CCGG could significantly decrease the levels of FFA, TG, TC, LDL-C, and LDL-C/HDL-C, AST, ALT, and ketone bodies in serum, and hepatic TG and TC contents, and increase the levels of HDL-C in serum and lipase activity in fat tissues compared to the HED group. Liver histopathology also showed that CCGG could significantly reduce the incidence of liver lesions. CONCLUSION: These results suggested that CCGG stimulated lipid metabolism in HED-induced obese rats, which is attributable to fat mobilization from adipose tissue.

Pre-diabetes alters testicular PGC1-α/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress.

Pre-diabetes, a risk factor for type 2 diabetes development, leads to metabolic changes at testicular level. Peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) and Sirtuin 3 (Sirt3) are pivotal in mitochondrial function. We hypothesized that pre-diabetes disrupts testicular PGC-1α/Sirt3 axis, compromising testicular mitochondrial function. Using a high-energy-diet induced pre-diabetic rat model, we evaluated testicular levels of PGC-1α and its downstream targets, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2), mitochondrial transcription factor A (TFAM) and Sirt3. We also assessed mitochondrial DNA (mtDNA) content, mitochondrial function, energy levels and oxidative stress parameters. Protein levels were quantified by Western Blot, mtDNA content was determined by qPCR. Mitochondrial complex activity and oxidative stress parameters were spectrophotometrically evaluated. Adenine nucleotide levels, adenosine and its metabolites (inosine and hypoxanthine) were determined by reverse-phase HPLC. Pre-diabetic rats showed increased blood glucose levels and impaired glucose tolerance. Both testicular PGC-1α and Sirt3 levels were decreased. NRF-1, NRF-2 and TFAM were not altered. Testicular mtDNA content was decreased. Mitochondrial complex I activity was increased, whereas mitochondrial complex III activity was decreased. Adenylate energy charge was decreased in pre-diabetic rats, as were ATP and ADP levels. Conversely, AMP levels were increased, evidencing a decreased ATP/AMP ratio. Concerning to oxidative stress pre-diabetes decreased testicular antioxidant capacity and increased lipid and protein oxidation. In sum, pre-diabetes compromises testicular mitochondrial function by repressing PGC-1α/Sirt3 axis and mtDNA copy number, declining respiratory capacity and increasing oxidative stress. This study gives new insights into overall testicular bioenergetics at this prodromal stage of disease.

The proteomic profile is altered but not repaired after bariatric surgery in type 2 diabetes pigs.

To reveal the sources of obesity and type 2 diabetes (T2D) in humans, animal models, mainly rodents, have been used. Here, we propose a pig model of T2D. Weaned piglets were fed high fat/high sugar diet suppling 150% of metabolizable energy. Measurements of weight gain, blood morphology, glucose plasma levels, cholesterol, and triglycerides, as well as glucose tolerance (oral glucose tolerance test, OGTT) were employed to observe T2D development. The histology and mass spectrometry analyses were made post mortem. Within 6 months, the high fat-high sugar (HFHS) fed pigs showed gradual and significant increase in plasma triglycerides and glucose levels in comparison to the controls. Using OGTT test, we found stable glucose intolerance in 10 out of 14 HFHS pigs. Mass spectrometry analysis indicated significant changes in 330 proteins in the intestine, liver, and pancreas of the HFHS pigs. These pigs showed also an increase in DNA base modifications and elevated level of the ALKBH proteins in the tissues. Six diabetic HFHS pigs underwent Scopinaro bariatric surgery restoring glycaemia one month after surgery. In conclusion, a high energy diet applied to piglets resulted in the development of hyperlipidaemia, hyperglycaemia, and type 2 diabetes being reversed by a bariatric procedure, excluding the proteomic profile utill one month after the surgery.

Effect of a Diet-Induced Obesity on the Progeny Response in a Murine Model.

Diet-induced obesity could have detrimental effects on adults and their progeny. The aim of this study was to determine the effect of a high-energy diet on both F1 mice body weight and tissue/organ weight and F2 offspring growth. A simple murine model for obesity was developed using a high-energy diet and mice reared in litters of five or ten, from 30 dams receiving a cafeteria diet of either commercial chow (low energy), or a mixture of commercial chow, chocolate (50% cacao), and salty peanuts (high energy). This diet continued from mating until weaning, when the pups were allocated according to sex into eight groups based on maternal diet, litter size, and post-weaning diet. On day 74, the males were slaughtered, and the females were bred then slaughtered after lactation. As a result, the high-energy maternal diet increased the F1 offspring growth during lactation, while the high-energy post-weaning diet increased the F1 adult body weight and tissue/organ weight. The high-energy maternal diet could negatively affect the onset of the F1 but not the maintenance of breastfeeding of F1 and F2 offspring. For F2 offspring growth, the high energy overlapped the low-energy post-weaning diet, due to problems of gaining weight during lactation.

Prenatal Cafeteria Diet Primes Anxiety-like Behavior Associated to Defects in Volume and Diffusion in the Fimbria-fornix of Mice Offspring.

Prenatal exposure to high-energy diets primes brain alterations that increase the risk of developing behavioral and cognitive failures. Alterations in the structure and connectivity of brain involved in learning and memory performance are found in adult obese murine models and in humans. However, the role of prenatal exposure to high-energy diets in the modulation of the brain's structure and function during cognitive decline remains unknown. We used female C57BL6 mice (n = 10) exposed to a high-energy diets (Cafeteria diet (CAF)) or Chow diet for 9 weeks (before, during and after pregnancy) to characterize their effect on brain structural organization and learning and memory performance in the offspring at two-month-old (n = 17). Memory and learning performance were evaluated using the Y-maze test including forced and spontaneous alternation, novel object recognition (NORT), open field and Barnes maze tests. We found no alterations in the short- or long-time spatial memory performance in male offspring prenatally exposed to CAF diet when compared to the control, but they increased time spent in the edges resembling anxiety-like behavior. By using deformation-based morphometry and diffusion tensor imaging analysis we found that male offspring exposed to CAF diet showed increased volume in primary somatosensory cortex and a reduced volume of fimbria-fornix, which correlate with alterations in its white matter integrity. Biological modeling revealed that prenatal exposure to CAF diet predicts low volume in the fimbria-fornix, which was associated with anxiety in the offspring. The findings suggest that prenatal exposure to high-energy diets prime brain structural alterations related to anxiety in the offspring.

Ascophyllum nodosum and Fucus vesiculosus Extracts Improved Lipid Metabolism and Inflammation in High-Energy Diet-Induced Hyperlipidemia Rats.

Ascophyllum nodosum and Fucus vesiculosus both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome. To date, no study has explored the antihyperlipidemic effects of phlorotannins from A. nodosum and F. vesiculosus in animal models. Therefore, in the present study, we investigated the effects of phlorotannins using a rat model of high-energy diet (HED)-induced hyperlipidemia. The results showed that the rats that were fed an HED and treated with phlorotannin-rich extract from A. nodosum and F. vesiculosus had significantly lower serum fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triacylglyceride (TG) and free fatty acids (FFAs) levels and hepatic TG level and had higher serum insulin, high-density lipoprotein cholesterol (HDL-C) levels and lipase activity in their fat tissues than in the case with the rats that were fed the HED alone. A histopathological analysis revealed that phlorotannin-rich extract could significantly reduce the size of adipocytes around the epididymis. In addition, the rats treated with phlorotannin-rich extract had significantly lowered interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities than did those in the HED group. These results suggested that the phlorotannin-rich extract stimulated lipid metabolism and may have promoted lipase activity in rats with HED-induced hyperlipidemia. Our results indicated that A. nodosum and F. vesiculosus, marine algae typically used as health foods, have strong antihyperlipidemic effects and may, therefore, be useful for preventing atherosclerosis. These algae may be incorporated into antihyperlipidemia pharmaceuticals and functional foods.

Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice.

Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic de novo lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.

Mechanisms of autophagic responses to altered nutritional status.

Autophagy is a dynamic process and critical for cellular remodeling and organelle quality control. In response to altered nutritional status (e.g., fasting and feeding), autophagic activity is finely tuned by transcriptional, posttranslational, and epigenetic regulations via various signaling pathways, including energy sensors (e.g., mechanistic target of rapamycin (mTOR)/ AMP-activated protein kinase - Unc-51 Like Autophagy Activating Kinase 1, mTORC1- WD Repeat Domain, Phosphoinositide Interacting 2, mTORC1- transcription factor EB, perilipin 5- Sirtuin 1, and Sirtuin 1-mediated deacetylation of autophagy proteins), fasting or feeding induced hormones (e.g., fibroblast growth factor [FGF21]- protein kinase A - Jumonji domain-containing protein D3, FGF21- downstream regulatory element antagonist modulator - E3 ligase Midline-1- transcription factor EB, FGF19-SHP- lysine-specific demethylase, insulin- insulin receptor substrate - protein kinase B - forkhead box O, glucagon- protein kinase A - cAMP response binding protein), and lysosomal enzymes (e.g., cathepsin B and cathepsin L). In contrast to fasting that induces autophagy and health benefits, nutrient oversupply (overfeeding or feeding on high energy diets) dysregulates autophagy, which has been increasingly observed in animal models of human chronic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Studies have revealed multifaceted effects of high energy diets on autophagy, being either an inhibitor or enhancer of autophagy. The conundrum may arise from the variations in methods for autophagy analysis, components of high energy diets and control diets for treatments, treatment durations, and the ages of genetic backgrounds of laboratory animals. In this article, we reviewed the evidence from both human and animal studies, presenting the molecular mechanism of autophagic response to altered nutritional status and discussing the contributing factors of and possible solution to the current conundrum concerning the exact role of high energy diets in autophagic regulation.

Evaluation of polyherbal formulation in broilers fed high energy diet: Implications on zootechnical parameters, fat accretion, and serum L-carnitine levels.

Objective: The current broiler trial was planned to assess the effects of Kolin Plus™, a polyherbal formulation (PHF), on performance, protein and fat accretion, and serum L-carnitine (LC) levels in broilers fed a high-energy diet (HED). Materials and Methods: A total of 500 1-day-old Cobb 430 male chicks were assigned to 5 treatment groups consisting of 10 replicates, with 10 birds in each replicate (n = 100). Group G1 was a negative control fed HED, and group G2, a positive control supplemented with synthetic choline chloride (SCC) 1,500 gm/ton in HED. Groups G3, G4, and G5 were supplemented with PHF in HED at 400, 500, and 750 gm/ton feed, respectively (PHF400, PHF500, and PHF750). Results: The PHF produced a dose-dependent numerical improvement in body weight, feed conversion ratio, livability, and the European Production Index. There were no changes in carcass nitrogen and protein accretion, whereas a statistically significant decrease (p < 0.05) in carcass fat and fat accretion was observed in the SCC and PHF groups. Moreover, PHF showed a significant increase in serum LC levels. Conclusion: Kolin Plus™ improves performance parameters akin to SCC by improving fat metabolism and mobilization by enhancing serum LC levels and restoring normal fat accretion.

Intramuscular collagen characteristics and expression of related genes in skeletal muscle of cull cows receiving a high-energy diet.

We aimed to investigate differences in the synthesis and metabolism of intramuscular collagen in the Longissimus thoracis (LT) muscle between heifers and cull-cows fed high-energy diet. Ten cull-cows, (74.9 ± 3.2 months age, weighing 536 ± 14.55 kg) and ten heifers (18.4 ± 3.2 months age, weighting 310.5 ± 14.5 kg) were fed with high-energy diets for 150 days. The total collagen content did not differ between treatments. Greater collagen solubility was observed in heifers than cull-cows, although no differences in lysyl oxidase activity were observed between treatments. No differences were observed for mRNA expression of CO1A1, MMP2, MMP9 and TIMP2 between treatments. However, cull-cows presented greater mRNA expression of COL3A1, TIMP1 and TIMP3 than heifers. Our data give no indication that feeding a high-energy diet to cull-cows decreases the concentration of intramuscular collagen in the LT muscle or increases its solubility in respect to the collagen solubility in LT muscles from heifers on the same diet.