Reduction in Cold Stress in an Innovative Metabolic Cage Housing System Increases Animal Welfare in Laboratory Mice.

Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress.

Postprandial dynamics and response of fibroblast growth factor 21 in older adults.

Background & Aims: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition.

The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells.

Objective: Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood.

FGF21, not GCN2, influences bone morphology due to dietary protein restrictions.

Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling.

Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH.

Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction.

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism.

Reduced dietary protein intake induces adaptive physiological changes in macronutrient preference, energy expenditure, growth, and glucose homeostasis. We demonstrate that deletion of the FGF21 co-receptor βKlotho (Klb) from the brain produces mice that are unable to mount a physiological response to protein restriction, an effect that is replicated by whole-body deletion of FGF21. Mice forced to consume a low-protein diet exhibit reduced growth, increased energy expenditure, and a resistance to diet-induced obesity, but the loss of FGF21 signaling in the brain completely abrogates that response.

Methionine restriction prevents onset of type 2 diabetes in NZO mice.

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans.

Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein.

Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components.

Dominance-diversity relationships in ant communities differ with invasion.

The relationship between levels of dominance and species richness is highly contentious, especially in ant communities. The dominance-impoverishment rule states that high levels of dominance only occur in species-poor communities, but there appear to be many cases of high levels of dominance in highly diverse communities. The extent to which dominant species limit local richness through competitive exclusion remains unclear, but such exclusion appears more apparent for non-native rather than native dominant species.

Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes.

Aims/hypothesis: Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism.

Methods: We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes.

Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease.

Objective: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity.

Low protein-induced increases in FGF21 drive UCP1-dependent metabolic but not thermoregulatory endpoints.

Dietary protein restriction increases adipose tissue uncoupling protein 1 (UCP1), energy expenditure and food intake, and these effects require the metabolic hormone fibroblast growth factor 21 (FGF21). Here we test whether the induction of energy expenditure during protein restriction requires UCP1, promotes a resistance to cold stress, and is dependent on the concomitant hyperphagia. Wildtype, Ucp1-KO and Fgf21-KO mice were placed on control and low protein (LP) diets to assess changes in energy expenditure, food intake and other metabolic endpoints.

FGF21 improves glucose homeostasis in an obese diabetes-prone mouse model independent of body fat changes.

Aims/hypothesis: Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes.

Methods: Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week.

A global database of ant species abundances.

What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51 ,388 ant abundance and occurrence records of more than 2,693 species and 7,953 morphospecies from local assemblages collected at 4,212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions.

Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2.

FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months.

Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number.

Protein-dependent regulation of feeding and metabolism.

Free-feeding animals often face complex nutritional choices that require the balancing of competing nutrients, but the mechanisms driving macronutrient-specific food intake are poorly defined. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake and metabolism, and that dietary protein intake may be prioritized over energy intake. This review focuses on recent progress in defining the mechanisms underlying protein-specific feeding.

Cerebrospinal fluid prohormone processing and neuropeptides stimulating feed intake of dairy cows during early lactation.

After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides.

FGF21 is an endocrine signal of protein restriction.

Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake.

Effects of parturition and feed restriction on concentrations and distribution of the insulin-like growth factor-binding proteins in plasma and cerebrospinal fluid of dairy cows.

Hormones and metabolites act as satiety signals in the brain and play an important role in the control of feed intake (FI). These signals can reach the hypothalamus and brainstem, 2 major centers of FI regulation, via the blood stream or the cerebrospinal fluid (CSF). During the early lactation period of high-yielding dairy cows, the increase of FI is often insufficient.

Concentrations of hormones and metabolites in cerebrospinal fluid and plasma of dairy cows during the periparturient period.

During early lactation, high-yielding dairy cows often show insufficient feed intake (FI) and, as a consequence, they enter into a negative energy balance associated with an altered pattern of plasma metabolites and hormones. These act as short- and long-term hunger or satiety signals in the brain and play an important role in the control of FI. Metabolites and hormones also occur in cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem, 2 major centers of FI regulation.

Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

Endocrines and metabolites in the circulation act as long-term hunger or satiety signals in the brain during negative energy balance and play an important role in the control of feed intake. These signals also occur in the cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed intake regulation. Thus CSF functions as a transport medium for fuel signals between blood and brain.

The ketone body β-hydroxybutyric acid influences agouti-related peptide expression via AMP-activated protein kinase in hypothalamic GT1-7 cells.

β-Hydroxybutyric acid (BHBA) acts in the brain to influence feeding behaviour, but the underlying molecular mechanisms are unclear. GT1-7 hypothalamic cells expressing orexigenic agouti-related peptide (AGRP) were used to study the AMP-activated protein kinase (AMPK) pathway known to integrate dietary and hormonal signals for food intake regulation. In a 25 mM glucose culture medium, BHBA increased intracellular calcium concentrations and the expression of monocarboxylate transporter 1 (MCT1 (SLC16A1)).