ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.

Background And Aims: Deficiency of the phospholipid transporter ATP8B1 causes infantile-onset progressive familial intrahepatic cholestasis type I (PFIC1). Pre-transplant PFIC1 patients often present with mild dyslipidaemia. This raises the possibility that PFIC1 patients, besides cholestasis, may also experience defects in glucose and lipid metabolism.

Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development.

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome.

Context: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with obesity, insulin resistance, and dyslipidemia. Hyperandrogenism is a major characteristic of PCOS. Increased androgen exposure is believed to deregulate metabolic processes in various tissues as part of the PCOS pathogenesis, predominantly through the androgen receptor (AR).

Combined GIP receptor and GLP1 receptor agonism attenuates NAFLD in male APOE∗3-Leiden.CETP mice.

Background: Combined glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP1R) agonism is superior to single GLP1R agonism with respect to glycemic control and weight loss in obese patients with or without type 2 diabetes. As insulin resistance and obesity are strong risk factors for nonalcoholic fatty liver disease (NAFLD), in the current study we investigated the effects of combined GIPR/GLP1R agonism on NAFLD development.

Methods: Male APOE∗3-Leiden.

Combined glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonism attenuates atherosclerosis severity in APOE*3-Leiden.CETP mice.

Background And Aims: Combined agonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP1R) is superior to single GLP1R agonism in terms of glycemic control and lowering body weight in individuals with obesity and with or without type 2 diabetes mellitus. As both GIPR and GLP1R signaling have also been implicated in improving inflammatory responses and lipid handling, two crucial players in atherosclerosis development, here we aimed to investigate the effects of combined GIPR/GLP1R agonism in APOE*3-Leiden.CETP mice, a well-established mouse model for human-like lipoprotein metabolism and atherosclerosis development.

Dietary butyrate ameliorates metabolic health associated with selective proliferation of gut Lachnospiraceae bacterium 28-4.

Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.

Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.

Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.

Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: A randomized cross-over trial.

Background: The application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold.

Methods: This secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.

Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans.

Brown adipocytes within brown adipose tissue (BAT) and beige adipocytes within white adipose tissue dissipate nutritional energy as heat. Studies in mice have shown that activation of thermogenesis in brown and beige adipocytes enhances the lipolytic processing of triglyceride-rich lipoproteins (TRLs) in plasma to supply these adipocytes with fatty acids for oxidation. This process results in formation of TRL remnants that are removed from the circulation through binding of apolipoprotein E (ApoE) on their surface to the LDL receptor (LDLR) on hepatocytes, followed by internalization.

A simplified procedure to trace triglyceride-rich lipoprotein metabolism in vivo.

Glycerol tri[ H]oleate and [ C]cholesteryl oleate double-labeled triglyceride-rich lipoprotein (TRL)-like particles are a well-established tool to trace the effect of lipid-modulating interventions on TRL metabolism. The routine generation of these particles involves sonication of a lipid mixture and subsequent fractionation of resulting particles into populations of different average size through density gradient ultracentrifugation. Here, we describe a simplified and more time-efficient procedure for preparing TRL-like particles without the need of fractionation.

Cannabinoid type 1 receptor inverse agonism attenuates dyslipidemia and atherosclerosis in APOE∗3-Leiden.CETP mice.

Pharmacological blockade of the cannabinoid type 1 receptor, a G protein-coupled receptor expressed in the central nervous system and various peripheral tissues, reverses diet-induced obesity and dyslipidemia through the reduction of food intake and altered nutrient partitioning. This strategy is being explored for a number of therapeutic applications; however, its potency for the treatment of atherosclerotic cardiovascular disease via improvements in lipid metabolism remains unclear. Therefore, here, we aimed to investigate whether inhibition of the endocannabinoid system can attenuate atherosclerosis development through improvement of dyslipidemia.

Hepatic Scavenger Receptor Class B Type 1 Knockdown Reduces Atherosclerosis and Enhances the Antiatherosclerotic Effect of Brown Fat Activation in APOE*3-Leiden.CETP Mice.

[Figure: see text].

Effects of dietary methionine supplementation on growth performance, intestinal morphology, antioxidant capacity and immune function in intra-uterine growth-retarded suckling piglets.

This study investigated the effects of dietary supplementation with -methionine ( -Met), -methionine ( -Met) and calcium salt of the methionine hydroxyl analog (MHA-Ca) on growth performance, intestinal morphology, antioxidant capacity and immune function in intra-uterine growth-retarded (IUGR) suckling piglets. Six normal birthweight (NBW) female piglets and 24 same-sex IUGR piglets were selected at birth. Piglets were fed nutrient adequate basal diet supplemented with 0.

Effects of dietary methionine restriction on postnatal growth, insulin sensitivity, and glucose metabolism in intrauterine growth retardation pigs at 49 and 105 d of age.

This study was conducted to investigate the effects of methionine restriction (MR) on growth performance, insulin sensitivity, and hepatic and muscle glucose metabolism in intrauterine growth retardation (IUGR) pigs at 49 and 105 d of age. At weaning (day 21), 30 female normal birth weight (NBW) piglets were fed control diets with adequate methionine (NBW-CON), whereas 60 female IUGR piglets were fed either the control diets (IUGR-CON) or MR diets which were 30% reduced in methionine (IUGR-MR) (n = 6 replicates (pens) with five piglets per replicate). At 49 and 105 d of age, one pig with a BW near to the mean of each replication was selected for biochemical analysis.

l-Threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets.

Objectives: The aim of this study was to investigate the effects of dietary l-threonine supplementation on the growth performance, intestinal immune function, mucin synthesis, and goblet cell differentiation in weanling piglets with intrauterine growth retardation (IUGR).

Methods: Eighteen litters of newborn piglets were selected at birth, with one normal birthweight (NBW) and two IUGR piglets in each litter. At weaning, the NBW piglet and one of the IUGR piglets were assigned to groups fed a basal diet (i.

Effects of dietary supplementation on growth performance, intestinal morphology, inflammatory response, and microbiota of intra-uterine growth retarded weanling piglets.

Background: The focus of recent research has been directed toward the probiotic potential of (BA) on the gut health of animals. However, little is known about BA's effects on piglets with intra-uterine growth retardation (IUGR). Therefore, this study investigated the effects of BA supplementation on the growth performance, intestinal morphology, inflammatory response, and microbiota of IUGR piglets.

Effects of Dietary Zinc Oxide Nanoparticles on Growth, Diarrhea, Mineral Deposition, Intestinal Morphology, and Barrier of Weaned Piglets.

This study was conducted to investigate effects of dietary zinc oxide nanoparticles (nano-ZnOs) on growth, diarrhea rate, mineral deposition (Zn, Fe, and Mn), intestinal morphology, and barrier of weaned piglets. A total of 384 weaned piglets (Duroc × Landrace × Yorkshire) in 4 groups were fed a basal diet supplemented with 0, 400, and 800 mg/kg nano-ZnOs or 3000 mg/kg ZnO for 14 days. Compared with the control group, 800 mg/kg nano-ZnOs and 3000 mg/kg ZnO significantly increased average daily gain and decreased diarrhea rate of weaned piglets.

Effects of dietary L-methionine supplementation on intestinal integrity and oxidative status in intrauterine growth-retarded weanling piglets.

Purpose: The present study investigated whether dietary methionine supplementation might protect against intrauterine growth retardation (IUGR)-induced damage in the intestine of piglets.

Methods: Thirty normal birth weight (NBW) female piglets and sixty same-sex IUGR piglets were weaned at 21 days of postnatal age and fed the control diet (4.0 g methionine per kg of feed, NBW-CON, and IUGR-CON groups) or the methionine-supplemented diet (5.

Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis.

Individuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW). This study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR.

Zinc oxide nanoparticles as a substitute for zinc oxide or colistin sulfate: Effects on growth, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets.

The objective of this study was to evaluate effects of zinc oxide nanoparticles (nano-ZnOs) as a substitute for colistin sulfate (CS) and/or zinc oxide (ZnO) on growth performance, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets. A total of 216 crossbred Duroc×(Landrace×Yorkshire) piglets weaned at 23 days were randomly assigned into 3 groups, which were fed with basal diets supplemented with 20 mg/kg CS (CS group), 20mg/kg CS+3000 mg/kg ZnO (CS+ZnO group), and 1200 mg/kg nano-ZnOs (nano-ZnO group) for 14 days. Results indicated that compared to CS group, supplementation of 1200 mg/kg nano-ZnOs (about 30 nm) significantly increased final body weight and average daily gain, and 3000 mg/kg ZnO plus colistin sulfate significantly increased average daily gain and decreased diarrhea rate in weaned piglets.

Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets.

Background/objectives: The study was conducted to evaluate the effects of dietary leucine supplementation on mitochondrial biogenesis and energy metabolism in the liver of normal birth weight (NBW) and intrauterine growth-retarded (IUGR) weanling piglets.

Materials/methods: A total of sixteen pairs of NBW and IUGR piglets from sixteen sows were selected according to their birth weight. At postnatal day 14, all piglets were weaned and fed either a control diet or a leucine-supplemented diet for 21 d.

Resveratrol attenuates mitochondrial dysfunction in the liver of intrauterine growth retarded suckling piglets by improving mitochondrial biogenesis and redox status.

Scope: Emerging evidence has identified mitochondrial biogenesis and oxidative phosphorylation as potential targets for the prevention and treatment of metabolic syndrome. This study investigated the effect of resveratrol (RSV) on hepatic mitochondrial function in intrauterine growth-retarded (IUGR) suckling piglets.

Methods And Results: Seven normal birth weight (NBW) and fourteen IUGR neonatal male piglets were selected.