Involvement of skeletal muscle protein, glycogen, and fat metabolism in the adaptation on early lactation of dairy cows

During early lactation, high-yielding dairy cows cannot consume enough feed to meet nutrient requirements. As a consequence, animals drop into negative energy balance and mobilize body reserves including muscle protein and glycogen for milk production, direct oxidation, and hepatic gluconeogenesis. To examine which muscle metabolic processes contribute to the adaptation during early lactation, six German Holstein cows were blood sampled and muscle biopsied throughout the periparturient period. From pregnancy to lactation, the free plasma amino acid pattern imbalanced and plasma glucose decreased. Several muscle amino acids, as well as total muscle protein, fat, and glycogen, and the expression of glucose transporter-4 were reduced within the first 4 weeks of lactation. The 2-DE and MALDI-TOF-MS analysis identified 43 differentially expressed muscle protein spots throughout the periparturient period. In early lactation, expression of cytoskeletal proteins and enzymes involved in glycogen synthesis and in the TCA cycle was decreased, whereas proteins related to glycolysis, fatty acid degradation, lactate, and ATP production were increased. On the basis of these results, we propose a model in which the muscle breakdown in early lactation provides substrates for milk production by a decoupled Cori cycle favoring hepatic gluconeogenesis and by interfering with feed intake signaling.     

High-protein diet during gestation and lactation affects mammary gland mRNA abundance, milk composition and pre-weaning litter growth in mice

We evaluated the effect of a high-protein diet (HP) on pregnancy, lactational and rearing success in mice. At the time of mating, females were randomly assigned to isoenergetic diets with HP (40% w/w) or control protein levels (C; 20%). After parturition, half of the dams were fed the other diet throughout lactation resulting in four dietary groups: CC (C diet during gestation and lactation), CHP (C diet during gestation and HP diet during lactation), HPC (HP diet during gestation and C diet during lactation) and HPHP (HP diet during gestation and lactation). Maternal and offspring body mass was monitored. Measurements of maternal mammary gland (MG), kidney and abdominal fat pad masses, MG histology and MG mRNA abundance, as well as milk composition were taken at selected time points. HP diet decreased abdominal fat and increased kidney mass of lactating dams. Litter mass at birth was lower in HP than in C dams (14.8 v. 16.8 g). Dams fed an HP diet during lactation showed 5% less food intake (10.4 v. 10.9 g/day) and lower body and MG mass. On day 14 of lactation, the proportion of MG parenchyma was lower in dams fed an HP diet during gestation as compared to dams fed a C diet (64.8% v. 75.8%). Abundance of MG α-lactalbumin, β-casein, whey acidic protein, xanthine oxidoreductase mRNA at mid-lactation was decreased in all groups receiving an HP diet either during gestation and/or lactation. Milk lactose content was lower in dams fed an HP diet during lactation compared to dams fed a C diet (1.6% v. 2.0%). On days 14, 18 and 21 of lactation total litter mass was lower in litters of dams fed an HP diet during lactation, and the pups' relative kidney mass was greater than in litters suckled by dams receiving a C diet. These findings indicate that excess protein intake in reproducing mice has adverse effects on offspring early in their postnatal growth as a consequence of impaired lactational function.     

Multi-block PCA and multi-compartmental study of the metabolic responses to intake of hydrolysed versus intact casein in C57BL/6J mice by NMR-based metabolomics

Recently we showed that exchanging intact casein with extensively hydrolysed casein in Western diets prevented diet-induced obesity in obesity-prone C57BL/6J mice. To gain further insight into the underlying mechanisms for the metabolic alterations induced by intake of hydrolysed casein, we performed an exploratory investigation using proton NMR spectroscopy, multi-block PCA (MBPCA) and a multi-compartment model including analyses of plasma, urine, faeces and tissue samples from mice fed diets with intact or hydrolysed casein and 16 or 32 energy% protein. The MBPCA superscores showed a clear separation between samples from mice fed intact and hydrolysed casein diets, respectively. Block loadings revealed that fecal fat content was higher, and tissue and plasma lipid levels were lower in mice fed hydrolysed casein diets compared with mice fed intact casein. Amino acid metabolism was also altered by dietary protein form, and levels of branched-chain amino acids were higher in faeces and urine and lower in plasma and spleen in mice fed hydrolysed protein. Moreover, hepatic levels of the sulphur-containing metabolites taurine and glutathione were increased in mice fed hydrolysed casein, and hepatic glycogen amount was increased in mice fed hydrolysed casein. In contrast, the levels of glucose and its metabolite lactate were reduced in faeces, liver and plasma. Taken together, NMR-based metabolomic analyses indicated that pathways within lipid, amino acid and carbohydrate metabolism were altered by intake of hydrolysed casein, and that these alterations are likely to be underlying mechanisms for the observed prevention against diet-induced obesity associated with hydrolysed casein intake.     

Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit

High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.     

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM.     

Intracerebroventricular leptin administration reduces food intake in pregnant and lactating mice

Leptin acts within the hypothalamus to diminish food intake. During pregnancy and lactation, both circulating leptin concentrations and food intake are elevated, suggesting an ineffectiveness of leptin to reduce food intake in these mice. Thus, this study tested the ability of intracerebroventricular (ICV) leptin administration to alter food intake during pregnancy and lactation. Mice during the first, second, and third trimesters of pregnancy, lactating mice on postpartum Day 7, and age-matched female mice were used. Plasma leptin concentrations averaged 2.9 +/- 0.3 ng/ml in control mice, increased steadily as pregnancy progressed (3.4 +/- 0.7, 29.8 +/- 4.5, and 40.5 +/- 0.7 ng/ml during the first, second, and third trimesters, respectively), and remained elevated on Day 7 postpartum (26.4 +/- 7.8 ng/ml). Mice were food deprived for 4 h, injected ICV with vehicle or leptin (1 micro g), and food intake was subsequently measured hourly for 3 hr, and after 24 hr. Vehicle-treated pregnant mice consumed marginally more food than cycling control mice, whereas nursing dams ate two to three times as much food as controls. As expected, ICV leptin administration reduced 24-hr food intake of control mice by 2 g, or approximately 50%. ICV-administered leptin was as effective in reducing food intake of pregnant and lactating mice as observed in control mice. Thus, the elevated circulating leptin concentrations observed in pregnant and nursing mice did not alter the ability of ICV-administered leptin to diminish food intake. High plasma concentrations of leptin-binding proteins observed during pregnancy, and probably during lactation, may limit the amount of endogenous leptin reaching the hypothalamus, and may consequently enable increases in food intake concomitant with elevated plasma leptin during these nutritionally demanding periods.     

Fat and Carbohydrate Intake over Three Generations Modify Growth,Metabolism and Cardiovascular Phenotype in Female Mice in an Age-Related Manner

Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.     

Effects of dietary macronutrient composition on the fasted plasma metabolome of healthy adult cats

Metabolomics assays have recently been used in humans for the identification of biomarkers for dietary assessment and diseases. The application of metabolomics to feline nutrition, however, has been very limited. The objective of this study was to identify how the feline blood metabolome changed in response to dietary macronutrient composition. Twelve adult domestic cats were fed four nutritionally complete diets [control, high-fat (HF), high-protein (HP), high-carbohydrate (HC)] at amounts to maintain ideal body weight and body condition score for 16 days. Overnight fasted plasma samples were collected on day 16 and subjected to liquid/gas chromatography and mass spectrometry. Principal component analysis showed that metabolite profiles of cats fed HP, HF, and HC dietary regimes formed distinct clusters. Cats fed the HP diet had a metabolite profile associated with decreased nucleotide catabolism, but increased amino acid metabolism and ketone bodies, indicating a greater use of protein and fat for energy. Cats fed the HP diet had a significant increase in metabolites associated with gut microbial metabolism. Cats fed the HF diet had metabolites indicative of increased lipid metabolism, including free fatty acids, monoacylglycerols, glycerol-3-phosphate, cholesterol, ketone bodies, and markers of oxidative stress. γ-glutamylleucine, 3-hydroxyisobutyrate, and 3-indoxyl sulfate were identified by random forest analysis to distinguish cats fed the three macronutrient-rich diets. In conclusion, macronutrient-rich diets primarily altered markers of amino acid and lipid metabolism, with little changes in markers of carbohydrate and energy metabolism. Moreover, the HP diet influenced several metabolites originating from gut microbial metabolism.     

Excessive Energy Intake Does Not Modify Fed‐state Tissue Protein Synthesis Rates in Adult Rats

The impact of chronic excessive energy intake on protein metabolism is still controversial. Male Wistar rats were fed ad libitum during 5 weeks with either a high‐fat high‐sucrose diet (HF: n = 9) containing 45% of total energy as lipids (protein 14%; carbohydrate 40% with 83.5% sucrose) or a standard diet (controls: n = 10). Energy intake and body weight were recorded. At the end of the experiment, we measured body composition, metabolic parameters (plasma amino acid, lipid, insulin, and glucose levels), inflammatory parameter (plasma α2‐macroglobulin), oxidative stress parameters (antioxidant enzyme activities, lipoperoxidation (LPO), protein carbonyl content in liver and muscle), and in vivo fed–state fractional protein synthesis rates (FSRs) in muscle and liver. Energy intake was significantly higher in HF compared with control rats (+28%). There were significant increases in body weight (+8%), body fat (+21%), renal (+41%), and epidydimal (+28%) fat pads in HF compared with control rats. No effect was observed in other tissue weights (liver, muscle, spleen, kidneys, intestine). Liver and muscle FSRs, plasma levels of lipids, glucose, insulin and α2‐macroglobulin, soleus and liver glutathione reductase and peroxidase acitivities, MnSOD activity, LPO, and protein carbonyl content were not altered by the HF diet. Only soleus muscle and liver Cu/ZnSOD activity and soleus muscle catalase activities were reduced in HF rats compared with control rats. Thus, chronic excessive energy intake and increased adiposity, in the absence of other metabolic alterations, do not stimulate fed‐state tissue protein synthesis rates.     

High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.     

Effect of Diets Containing Sucrose vs. D‐tagatose in Hypercholesterolemic Mice

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D‐tagatose (TAG; an isomer of fructose currently used as a low‐calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low‐density lipoprotein receptor deficient (LDLr^−/−) mice. LDLr^−/− male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG‐fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR‐fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR‐fed mice compared to TAG and CONTROL. Male and female SUCR‐fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR‐fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR‐fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.     

Beyond lipids, pharmacological PPARalpha activation has important effects on amino acid metabolism as studied in the rat

PPARalpha agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARalpha agonist WY 14,643 (30 micromol x kg(-1) x day(-1) for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARalpha activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.     

Increasing protein at the expense of carbohydrate in the diet down-regulates glucose utilization as glucose sparing effect in rats

High protein (HP) diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP) on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein) for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein) for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD). Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1(st) day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets.     

The significance of hyperphagia and diet composition on the metabolism in ventromedial hypothalamic lesioned male rats

The metabolic consequences of ventromedial hypothalamic lesion were studied in a group of aged male rats which were obese and had decreased response to insulin. The effects of hyperphagia and ventromedial hypothalamic lesion per se were separated by comparing experimental animals fed isocalorically with controls and animals fed ad libitum. Ventromedial hypothalamic lesion as such led to increases in the glucose conversion to fatty acid and in lipoprotein lipase activity in adipose tissue. Protein catabolism as reflected by plasma urea levels, was enhanced. The lipoprotein lipase activity in heart tended to be lower after VMH lesion. These metabolic changes were amplified in the VMH lesioned rats fed ad libitum. The liver glycogen content was lowered by VMH lesion, but this effect was abolished by hyperphagia. In parallel experiments the influence of diet composition was studied by feeding similar groups with diet of high fat content. The glucose incorporation in fatty acids was in all groups markedly and similarly inhibited by the high fat diet. The increase in lipoprotein lipase activity in heart and adipose tissue of control rats with high fat intake could not be demonstrated in any of the groups with ventromedial hypothalamic lesion. The plasma urea level in the control group was not affected by the diet, but tended to increase in the ventromedial hypothalamic lesioned groups on high fat intake. These findings demonstrate that the well known metabolic effects of ventromedial hypothalamic lesions are also manifest in obese insulin resistant male rats. Furthermore, the responses to changes in diet composition are different from those of the control rats.     

Carbohydrate—Fat Interactions and Obesity Examined by a Two‐Compartment Computer Model

Objective: A systems dynamics computer model was developed to examine how the interactions between carbohydrate and fat metabolism influence body weight regulation. It reflects the operation of a two reservoir‐system: one representing the body's limited glycogen, and the other, its large fat reserves. The outflows from the reservoirs correspond to the oxidation of glucose and fat, whose relative contributions are affected by the size of the prevailing glycogen and fat reserves. Together, they meet the body's energy expenditure. Replenishments occur three times per day, in portions restoring total glycogen content to specific levels. A parameter mimicking the action of insulin is necessary to create realistic responses. Research Methods and Procedures: The model was run for 125‐day periods to establish the degree of adiposity for which rates of fat oxidation become commensurate with fat intake and the influence thereon of various dietary, environmental, lifestyle, and inherited variables. Results: Equivalent degrees of adiposity can be sustained under a variety of conditions. For instance, the impact on steady‐state body fat contents of a 10% increase or decrease in the energy provided by dietary fat is offset by a 26‐gram decrease or increase in mean glycogen levels. Discussion: Environmental factors such as food diversity, palatability, and availability can be expected to raise the range within which glycogen levels are habitually maintained. This restrains fat oxidation, until expansion of the fat mass is sufficient to promote fat oxidation to a rate commensurate with dietary fat intake. This metabolic leverage can explain why increased food offerings tend to raise the prevalence of obesity.     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

Dietary <Emphasis Type="SmallCaps">l</Emphasis>-leucine and <Emphasis Type="SmallCaps">l</Emphasis>-alanine supplementation have similar acute effects in the prevention of high-fat diet-induced obesity

High-protein diets have been shown to alleviate detrimental effects of high-fat diets and this effect can be partially mimicked by dietary l-leucine supplementation. Here, we aimed to elucidate the early mechanisms and the specificity of leucine effects. We performed a 1-week trial with male C57BL/6 mice fed ad libitum with semisynthetic high-fat diets containing an adequate (10 % w/w, AP) or high (50 % w/w, HP) amount of whey protein, or supplemented with l-leucine corresponding to the leucine content within the HP diet (Leu) or supplemented with equimolar l-alanine (Ala). Food and water intake were monitored continuously using a computer-controlled monitor system and body composition changes were assessed using quantitative NMR. HP completely prevented the AP-induced accumulation of body fat. Leu and Ala resulted in a similar reduction of body fat accumulation which was intermediate between AP and HP. There were no significant effects on plasma glucose or insulin. Triacylglycerol content and gene expression of lipogenesis enzymes in liver as well as plasma cholesterol were reduced by HP compared to AP with Leu and Ala again showing intermediate effects. Body fat gain and liver triacylglycerols were strongly correlated with total energy intake. Water intake was rapidly increased by HP feeding and total water intake correlated strongly with total amino nitrogen intake. We concluded that the positive effects of high-protein diets on metabolic syndrome associated traits are acutely due to effects on satiety possibly linked to amino nitrogen intake and on the subsequent suppression of liver lipogenesis without evidence for a specific leucine effect.     

Effects of a high lipidic diet on murine energetic reserves in food deprivation

Female mice were fed for one month either control or cafeteria diets. Then they were subjected to food deprivation for up to 36 hours and their weight loss, tissue lipid, glycogen and protein were determined together with their plasma glycose, amino acids, urea, lipoproteins and ketone bodies. Cafeteria mice were able to cope with prolonged starvation with altered plasma composition and important loss of lipids and protein, sparing to a certain degree their glucose and amino acids. Control-fed mice, however, showed a intense ketosis and significant losses of nitrogen. The results obtained showed a higher ability of cafeteria mice to handle and use lipids, that evolves in a better suitability to resist food deprivation with less extensive alterations in their fuel and nitrogen homeostasis.