Energy Excretion Research Articles

Enzymatically Modified Starch Favorably Modulated Intestinal Transit Time and Hindgut Fermentation in Growing Pigs.

Aside from being used as stabilizing agents in many processed foods, chemically modified starches may act as functional dietary ingredients. Therefore, development of chemically modified starches that are less digestible in the upper intestinal segments and promote fermentation in the hindgut receives considerable attention. This study aimed to investigate the impact of an enzymatically modified starch (EMS) on nutrient flow, passage rate, and bacterial activity at ileal and post-ileal level. Eight ileal-cannulated growing pigs were fed 2 diets containing 72% purified starch (EMS or waxy cornstarch as control) in a cross-over design for 10 d, followed by a 4-d collection of feces and 2-d collection of ileal digesta. On d 17, solid and liquid phase markers were added to the diet to determine ileal digesta flow for 8 h after feeding. Reduced small intestinal digestion after the consumption of the EMS diet was indicated by a 10%-increase in ileal flow and fecal excretion of dry matter and energy compared to the control diet (P<0.05). Moreover, EMS feeding reduced ileal transit time of both liquid and solid fractions compared to the control diet (P<0.05). The greater substrate flow to the large intestine with the EMS diet increased the concentrations of total and individual short-chain fatty acids (SCFA) in feces (P<0.05). Total bacterial 16S rRNA gene abundance was not affected by diet, whereas the relative abundance of the Lactobacillus group decreased (P<0.01) by 50% and of Enterobacteriaceae tended (P<0.1) to increase by 20% in ileal digesta with the EMS diet compared to the control diet. In conclusion, EMS appears to resemble a slowly digestible starch by reducing intestinal transit and increasing SCFA in the distal large intestine.

Dietary fat and gut microbiota interactions determine diet-induced obesity in mice

ObjectiveGut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. MethodsGF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. ResultsGF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes) as a characteristic feature of normal SPF mice fed lard. ConclusionsIn conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.

Importance of the fat content within the cheese-matrix for blood lipid profile, faecal fat excretion, and gut microbiome in growing pigs

Cheese and butter have been shown to affect blood lipids differently. This parallel-arm, randomised, controlled study in 36 crossbred growing sows compared the effect of diets with either regular-fat cheese (REG), reduced-fat cheese + butter (RED) or butter (BUT) on blood lipids, faecal fat and energy excretion and gut microbiome in pigs. A 14-d run-in period was followed by 14-d interventions with macronutrient-matched diets. Fasting total cholesterol and HDL-cholesterol after 14 days were higher in REG compared with BUT, but only tended to be higher in RED. Compared with BUT, REG and RED had higher faecal fat excretion. Faecal energy excretion was only higher in REG, and this correlated with a lower microbiome Firmicutes-to-Bacteroidetes ratio. In conclusion, dairy fat consumed as cheese or butter caused different metabolic effects. Differences between reduced-fat cheese+butter and butter were less pronounced than differences between regular-fat cheese and butter, suggesting an impact of the dairy-matrix.

Effects of Dietary Protein Level on Nitrogen and Energy Budget of Juvenile Chinese Soft‐shelled Turtle, Pelodiscus sinensis, Wiegmann

AbstractThe effects of dietary protein level on nutrient digestibility and utilization of protein and energy of juvenile Chinese soft‐shelled turtle, Pelodiscus sinensis, were investigated. Seven isoenergetic diets containing graded levels of protein (25, 27, 29, 31, 33, 35, and 43%) were fed to turtles initially averaging 4.8 ± 0.7 g for 8 wk at 30 ± 0.5 C. The apparent digestibilities of dry matter, protein, and energy were generally increased with dietary protein level. Proportions of nitrogen intake (CN) allocated to excretory nitrogen (UN) were higher in 25 and 43% protein diets than the other diets. UN proportion was lowest in the 33% protein diet, whereas retained (growth) nitrogen (RN) followed an inverse pattern with UN. Percentages of gross energy intake (IE) used for excretory energy (UE) generally increased when dietary protein levels increased. Turtles fed 25–29% protein diets showed a markedly higher proportion of metabolizable energy (ME) than those fed 31–43% protein diets. Analysis by second‐order polynomial regression using RN as the indicator indicated that the estimated optimal dietary protein level was 34.6%. The lowest and highest percentages of retained (growth) energy (RE) were observed in the 25 and 33% protein groups. Nitrogen and energy budget equations of turtles fed 33% protein diet were 100 CN = 8.22 FN + 37.48 UN + 54.30 RN and 100 IE = 10.88 FE + 2.82 UE + 65.60 ME + 20.69 RE, respectively. Diets with excessive protein resulted in high proportions of protein and energy used for excretion.

17α-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization.

Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17β-estradiol (17β-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17α-E2 on nutrient-sensing pathways in visceral adipose tissue. 17α-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17α-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17α-E2. 17α-E2 increased AMPKα and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17α-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue-specific effects.

Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.

Effects of Cellulase Supplementation on Nutrient Digestibility, Energy Utilization and Methane Emission by Boer Crossbred Goats.

This study examined the effect of supplementing exogenous cellulase on nutrient and energy utilization. Twelve desexed Boer crossbred goats were used in a replicated 3×3 Latin square design with 23-d periods. Dietary treatments were basal diet (control, no cellulase), basal diet plus 2 g unitary cellulase/kg of total mixed ration dry matter (DM), and basal diet plus 2 g compound cellulase/kg of total mixed ration DM. Three stages of feeding trials were used corresponding to the three treatments, each comprised 23 d, with the first 14 d as the preliminary period and the following 9 d as formal trial period for metabolism trial. Total collection of feces and urine were conducted from the 4th d of the formal trial, and gas exchange measures were determined in indirect respiratory chambers in the last 3 d of the formal trial. Results showed that cellulase addition had no effect (p>0.05) on nutrient digestibility. Dietary supplementation of cellulase did not affect (p>0.05) N intake and retention in goats. Gross energy (GE) intake, fecal energy and urinary energy excretion, heat production were not affected (p>0.05) by the cellulase supplementation. Total methane emission (g/d), CH4 emission as a proportion of live weight or feed intake (DM, organic matter [OM], digestible DM or digestible OM), or CH4 energy output (CH4-E) as a proportion of energy intake (GE, digestible energy, or metabolizable energy), were similar (p>0.05) among treatments. There was a significant (p<0.001) relationship between CH4 and live weight (y = 0.645x+0.2, R2 = 0.54), CH4 and DM intake (y = 16.7x+1.4, R2 = 0.51), CH4 and OM intake (y = 18.8x+1.3, R2 = 0.51) and CH4-E and GE intake. Results from this study revealed that dietary supplementation of cellulase may have no effect on nutrient digestibility, nitrogen retention, energy metabolism, and methane emission in goat.

Addition of a worm leachate as source of humic substances in the drinking water of broiler chickens.

The objective of this research was to evaluate the growth performance, the apparent ileal digestibility of nitrogen and energy, the retention of nutrients and the apparent metabolizable energy corrected to zero nitrogen retention (AMEn) in broiler chickens supplemented with increasing doses of a worm leachate (WL) as a source of humic substances (HS) in the drinking water. In Exp. 1, 140 male broilers were penned individually and assigned to four WL levels (0%, 10%, 20%, and 30%) mixed in the drinking water from 21 to 49 days of age. Water was offered in plastic bottles tied to the cage. In Exp. 2, 600 male broilers from 21 to 49 days of age housed in floor pens were assigned to three levels of WL (0%, 10%, and 20%) mixed in the drinking water. The WL was mixed with tap water in plastic containers connected by plastic tubing to bell drinkers. The results of both experiments were subjected to analysis of variance and polynomial contrasts. In Exp. 1, the daily water consumption was similar among treatments but the consumption of humic, fulvic, and total humic acids increased linearly (p<0.01) as the WL increased in the drinking water. The feed conversion (p<0.01) and the ileal digestibility of energy, the excretion of dry matter and energy, the retention of dry matter, ash and nitrogen and the AMEn showed quadratic responses (p<0.05) relative to the WL levels in drinking water. In Exp. 2, the increasing level of WL in the drinking water had quadratic effects on the final body weight, daily weight gain and feed conversion ratio (p<0.05). The addition of WL as a source of HS in the drinking water had beneficial effects on the growth performance, ileal digestibility of energy, the retention of nutrients as well on the AMEn in broiler chickens; the best results were observed when the WL was mixed at levels of 20% to 30% in the drinking water.

Growth and energy budget of juvenile lenok Brachymystax lenok in relation to ration level

We evaluated the effect of ration level (RL) on the growth and energy budget of lenok Brachymystax lenok. Juvenile lenok (initial mean body weight 3.06±0.13 g) were fed for 21 d at five different ration levels: starvation, 2%, 3%, 4% bwd (body weight per day, based on initial mean values), and apparent satiation. Feed consumption, apparent digestibility, and growth were directly measured. Specific growth rates in terms of wet weight, dry weight, protein, and energy increased logarithmically with an increase in ration levels. The relationship between specific growth rate in terms of wet weight (SGRw, %/d) and RL (%) was characterized by a decelerating curve: SGRw=−1.417+3.166ln(RL+1). The apparent digestibility coefficients of energy exhibited a decreasing pattern with increasing ration level, and there was a significant difference among different RLs. Body composition was significantly affected by ration size. The relationship between feed efficiency rate in terms of energy (FERe) and RL was: FERe=−14.167+23.793RL-3.367(RL)2, and the maximum FERe was observed at a 3.53% ration. The maintenance requirement for energy of juvenile lenok was 105.39 kJ BW (kg)−0.80/d, the utilization efficiency of DE for growth was 0.496. The energy budget equation at satiation was: 100IE=29.03FE+5.78(ZE+UE)+39.56 HE+25.63 RE, where IE is feed energy, FE is fecal energy, ZE+UE is excretory energy, HE is heat production, and RE is recovered energy. Our results suggest that the most suitable feeding rate for juvenile lenok aquaculture for wet weight growth is 2.89% bwd, whereas for energy growth, the suggested rate is 3.53% bwd at this growth stage.

Effect of rye bread enriched with tomato pomace on fat absorption and lipid metabolism in rats fed a high-fat diet.

Tomato pomace (TP), obtained as a residue of tomato processing, was used to enrich rye bread (RB). The sensory profile of this functional bread (RB+TP) was characterised, and its fat absorption and lipid metabolism properties in high-fat-fed rats were studied. Intake of the HF diet containing RB, RB+TP, or TP alone increased faecal energy and fat excretion, but did not affect animal growth or visceral fat weight. Both RB and RB+TP diminished the negative impact of the HF diet, lowering the atherogenic index of plasma (AIP) and the total liver lipid contents by 31.6% and 24%, respectively. The experimental diets had no effect on liver S-adenosylhomocysteine (SAH) concentrations or on the S-adenosylmethionine (SAM) to SAH ratio, though the lowest SAM levels were observed in the HF+TP group. No significant differences were detected in blood homocysteine, triglycerides, glucose or insulin levels. Although RB+TP incorporated into a HF diet may lead to a decrease in AIP and total liver lipid content, this effect does not depend on the components of TP, but rather on the RB ingredients. However, pure TP, in the doses used in this study, may potentially play a role in the energy balance via faecal loss of lipids.

Energy and nutrient deposition and excretion in the reproducing sow: Model development and evaluation1

Air and nutrient emissions from swine operations raise environmental concerns. During the reproduction phase, sows consume and excrete large quantities of nutrients. The objective of this study was to develop a mathematical model to describe energy and nutrient partitioning and predict manure excretion and composition and methane emissions on a daily basis. The model was structured to contain gestation and lactation modules, which can be run separately or sequentially, with outputs from the gestation module used as inputs to the lactation module. In the gestating module, energy and protein requirements for maintenance, and fetal and maternal growth were described. In the lactating module, a factorial approach was used to estimate requirements for maintenance, milk production, and maternal growth. The priority for nutrient partitioning was assumed to be in the order of maintenance, milk production, and maternal growth with body tissue losses constrained within biological limits. Global sensitivity analysis showed that nonlinearity in the parameters was small. The model outputs considered were the total protein and fat deposition, average urinary and fecal N excretion, average methane emission, manure carbon excretion, and manure production. The model was evaluated using independent data sets from the literature using root mean square prediction error (RMSPE) and concordance correlation coefficients. The gestation module predicted body fat gain better than body protein gain, which was related to predictions of body fat and protein loss from the lactation model. Nitrogen intake, urine N, fecal N, and milk N were predicted with RMSPE as percentage of observed mean of 9.7, 17.9, 10.0, and 7.7%, respectively. The model provided a framework, but more refinements and improvements in accuracy of prediction (particularly urine N) are required before the model can be used to assess environmental mitigation options from sow operations.

Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis.

Several nuclear receptors regulate diverse metabolic functions that impact on critical biological processes, such as development, differentiation, cellular regeneration, and neoplastic conversion. In the liver, some members of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics. Excess energy burning resulting from increases in fatty acid oxidation systems in liver generates reactive oxygen species, and the resulting oxidative damage influences liver regeneration and liver tumor development. These nuclear receptors are important sensors of exogenous activators as well as receptor-specific endogenous ligands. In this regard, gene knockout mouse models revealed that some lipid-metabolizing enzymes generate PPARα-activating ligands, while others such as ACOX1 (fatty acyl-CoA oxidase1) inactivate these endogenous PPARα activators. In the absence of ACOX1, the unmetabolized ACOX1 substrates cause sustained activation of PPARα, and the resulting increase in energy burning leads to hepatocarcinogenesis. Ligand-activated nuclear receptors recruit the multisubunit Mediator complex for RNA polymerase II-dependent gene transcription. Evidence indicates that the Med1 subunit of the Mediator is essential for PPARα, PPARγ, CAR, and GR signaling in liver. Med1 null hepatocytes fail to respond to PPARα activators in that these cells do not show induction of peroxisome proliferation and increases in fatty acid oxidation enzymes. Med1-deficient hepatocytes show no increase in cell proliferation and do not give rise to liver tumors. Identification of nuclear receptor-specific coactivators and Mediator subunits should further our understanding of the complexities of metabolic diseases associated with increased energy combustion in liver.

Effects of (−)-epicatechin on a diet-induced rat model of cardiometabolic risk factors

Overweight and obesity have been associated with increase in cardiometabolic risk. Therapeutics include lifestyle changes and/or pharmacologic agents. However, such interventions are often limited by poor compliance and/or significant side effects. The consumption of certain dietary products, such as cocoa, exerts positive effects on cardiometabolic risk factors. (−)-Epicatechin (EPI), the most abundant flavonoid in cacao has been reported to replicate such effects. However its mechanisms of action have not been fully elucidated.In a rat model of high-fat diet-induced obesity and its associated crdiometabolic risk factors, we administered 1mg/kg of EPI, by gavage, for 2 weeks. Endpoints included weight-gain, glycemia, triglyceridemia, and systolic blood pressure. We also assessed food intake and fecal excretion. Mitochondrial function and structure related proteins were measured by Westerns.Obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension were developed after the administration of the high-fat diet for five weeks. EPI significantly decreased the rate of weight gain, glycemia and hypertriglyceridemia. The ratio between energy intake and excretion was not significantly modified by treatment. EPI restored the obesity-induced decreases in the levels of skeletal muscle and abdominal tissue sirtuins (SIRTs), peroxisome proliferator-activated receptor coactivator (PGC-1α), mitofilin, transcription factor A mitochondrial (TFAM), uncoupling protein 1 (UCP1), and deiodinase.EPI treatment yielded beneficial effects on high fat diet-induced endpoints thus may be considered as a potential agent for the treatment of obesity and its cardiometabolic associated abnormalities. Mechanism of action may be attributed to the modulation of cellular/mitochondrial function, thus improving overall metabolism.

Effects of low carbohydrate diets on energy and nitrogen balance and body composition in rats depend on dietary protein-to-energy ratio

ObjectivesTruly ketogenic rodent diets are low in carbohydrates but also low in protein. The aim of this study was to differentiate effects of ketosis, low carbohydrate (LC) and/or low-protein intake on energy and nitrogen metabolism. MethodsWe studied the nitrogen balance of rats fed LC diets with varying protein contents: LC diets consisted of 75/10, 65/20 and 55/30 percent of fat to protein (dry matter), respectively, and were iso-energetically pair-fed to a control (chow) diet to 12-wk-old male Wistar rats (n = 6 per diet).Previous studies demonstrated only LC75/10 was truly ketogenic. Food, fecal, and urine samples, as well as carcasses were collected and analyzed for heat of combustion and nitrogen (Kjeldahl method). Blood samples were analyzed for plasma protein, albumin, and triacylglycerol. ResultsAll LC groups displayed less body weight gain, and the degree of reduction was inversely related to digestible crude protein intake (daily weight gain compared with chow: LC75/10: −50%; LC55/30: −20%). Nitrogen excretion by urine was related to digestible protein intake (chow: 0.23 ± 0.02 g nitrogen/d; LC75/10: 0.05 ± 0.01 g nitrogen/d). Renal energy excretion was closely associated with intake of digestible crude protein (r = 0.697) and renal nitrogen excretion (r = 0.769). Energy-to-nitrogen ratio in urine was nearly doubled with LC75/10 compared with all other groups. Total body protein was highest with chow and lowest with LC75/10. Rats fed with LC75/10 displayed features of protein deficiency (reduced growth and nitrogen balance, hypoproteinemia, depletion of body protein, and increased body and liver fat), whereas the effects with the non-ketogenic diets LC65/20 and LC55/30 were less pronounced. ConclusionThese results suggest that truly ketogenic LC diets in growing rats are LC diets that are also deficient in protein for growth.

Extracted Oat and Barley β-Glucans Do Not Affect Cholesterol Metabolism in Young Healthy Adults1-4

β-Glucans are known to exhibit hypocholesterolemic effects. Increased intestinal viscosity is thought to be crucial for cholesterol lowering. It is suggested that concentration, molecular mass, and structure, including the ratio of (1→3) to (1→4) glucan bonds in the molecule, are of importance for β-glucan functionality. This study investigated the effects of 3 different β-glucan sources, incorporated into a beverage and yogurt, on blood lipids and fecal endpoints. Fourteen participants completed this randomized, crossover, single-blinded study with four 3-wk periods: control and 3.3 g/d oat, barley, and barley mutant β-glucans of similar molecular mass. Before and after each period, fasting and postprandial blood samples were drawn and 3-d fecal samples were collected. Treatment did not affect changes in total, LDL, and HDL cholesterol compared with control; however, consumption of 3.3 g/d of oat β-glucans for 3 wk resulted in greater decreases in total (−0.29 ± 0.09 mmol/L, P < 0.01), LDL (−0.23 ± 0.07 mmol/L, P < 0.01), and HDL (−0.05 ± 0.03 mmol/L, P < 0.05) cholesterol compared with baseline. Changes in LDL in the β-glucan treatments were not related to β-glucan structure (cellotriosyl:cellotetraosyl). Decreases in fasting triacylglycerol were substantially greater after oat β-glucan treatment compared with control (P = 0.03). Fecal dry and wet weight, stool frequency, fecal pH, and energy excretion were unaffected. The results do not fully support the hypocholesterolemic effects by differently structured oat and barley β-glucans. However, substantial differences compared with baseline suggest a potential for oat β-glucan, presumably due to its higher solubility and viscosity. This underlines the importance of elusive structural β-glucan features for beneficial physiologic effects.

Loss of Krüppel-Like Factor 3 (KLF3/BKLF) Leads to Upregulation of the Insulin-Sensitizing Factor Adipolin (FAM132A/CTRP12/C1qdc2)

Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3+/+ and Klf3−/− tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3−/− mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.

Trefoil factor family member 2 (Tff2) KO mice are protected from high‐fat diet‐induced obesity

Trefoil factor family member 2 (Tff2) is a small gut peptide, mainly known for its protective and healing functions. As previously demonstrated, high-fat (HF) feeding can rapidly and specifically modulate Tff2 transcription in key tissues of mice, including the duodenum and mesenteric adipose tissue, therefore suggesting a novel role for this gene in energy balance. To explore whether and how Tff2 can influence feeding behavior and energy metabolism, Tff2 knock-out (KO) mice were challenged with HF diet for 12 weeks, hence food and energy intakes, body composition, as well as energy excretion and serum lipid and hormonal levels were analyzed. Finally, energy efficiency was estimated. Tff2 KO mice showed a greater appetite and higher energy intake compared to wild-type (WT). Consistently, they presented lower levels of serum leptin, and increased transcription of agouti-related protein (Agrp) in the hypothalamus. Though energy and triglyceride fecal excretion were augmented in Tff2 KO mice, digestible energy intake was superior. However, KO mice were finally protected from HF diet-induced obesity, and accumulated less weight and fat depots than WT animals, while keeping a normal lean mass. Energy efficiency was lower in HF-KO mice, while energy expenditure and locomotor activity were globally increased. The present work demonstrates previously unsuspected roles for Tff2 and suggests it to be a mastermind in the control of energy balance and a promising therapeutic target for obesity.

May rye bread enriched with green tea extract be useful in the prevention of obesity in rats?

We examined the hypothesis that rye bread enriched with green tea extract (GTE) (at two different doses) can prevent obesity as a component of a hypercaloric diet by decreasing the absorption of energy providing nutrients and regulating lipid metabolism-related hormones, in comparison with normal caloric diet used in the Wistar rats. Adult male Wistar rats were divided into 4 groups: group ND received a normal caloric diet, group HRB received a hypercaloric diet with control rye bread, groups HRB0.8% and HRB1.1% received a hypercaloric diet with rye bread enriched with 0.8% and 1.1% GTE, respectively. Higher food intake in the ND group compared with the other groups of rats was noted; however, there was no statistical difference in the energy intake among any of the groups. Consumption of the hypercaloric diet increased the body weight of the rats (in comparison with ND), but rats from HRB1.1% group showed a tendency towards smaller gains in body weight (∼4.0%) when compared to the HRB group. The addition of 1.1% GTE to rye bread resulted in an increase in the energy content of faeces, compared to both HRB and ND groups. No differences were observed in plasma leptin concentrations between the four groups. The insulin level in rats fed a hypercaloric diet was higher in comparison to rats from the ND group. The consumption of rye bread enriched with 1.1% GTE may increase faeces energy excretion, but without significantly suppressing body weight gain, visceral fat accumulation, or changing biochemical parameters related to lipid metabolism.

High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects

BackgroundWhole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets.ObjectiveIn the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time.DesignTen participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents.ResultsThe results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.

Energy loss via urine and faeces – a combustive analysis in diabetic rats and the impact of antidiabetic treatment on body weight

Intensive glycaemic control in type 2 diabetes achieved by insulin is generally accompanied by body weight gain. This study was performed to emphasize the meaning of caloric analysis of urine and faeces for energy balance. We measured energetic loss via urine and faeces during antihyperglycaemic treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for 10 days with the sodium-glucose-linked transporter-2 (SGLT2) inhibitor AVE2268, with insulin glargine, with the GLP-1 receptor agonist lixisenatide and with the combination of insulin glargine and lixisenatide. Each study was accompanied by one lean (Fa/?) and one obese (fa/fa) untreated non-diabetic and diabetic control group, respectively. Blood glucose, body weight alterations and food assimilation efficiency were monitored. In control ZDF rats, more than 12 g/day of pure glucose was urinarily excreted. In total, the energetic loss via urine exceeded 30% from total energy uptake. Insulin glargine treatment decreased urinary energetic loss, leading to a body weight gain of approximately 3 g/day. An almost body weight-neutral antihyperglycaemic treatment could be achieved with AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose and thus energy excretion. Combining insulin glargine with lixisenatide attenuated the anabolic effect of insulin resulting in weight neutrality. Our data clearly show renal contribution to the body's energy control by urinary glucose excretion (UGE) during antidiabetic treatment. The undesired retained energy could be reduced via additional UGE or via simultaneous reduction of energy uptake and/or energy retention.