Dietary energy partition: the central role of glucose

Humans have developed effective survival mechanisms under conditions of nutrient (and energy) scarcity. Nevertheless, today, most humans face a quite different situation: excess of nutrients, especially those high in amino-nitrogen and energy (largely fat). The lack of mechanisms to prevent energy overload and the effective persistence of the mechanisms hoarding key nutrients such as amino acids has resulted in deep disorders of substrate handling. There is too often a massive untreatable accumulation of body fat in the presence of severe metabolic disorders of energy utilization and disposal, which become chronic and go much beyond the most obvious problems: diabetes, circulatory, renal and nervous disorders included loosely within the metabolic syndrome. We lack basic knowledge on diet nutrient dynamics at the tissue-cell metabolism level, and this adds to widely used medical procedures lacking su cient scientific support, with limited or nil success. In the present longitudinal analysis of the fate of dietary nutrients, we have focused on glucose as an example of a largely unknown entity. Even most studies on hyper-energetic diets or their later consequences tend to ignore the critical role of carbohydrate (and nitrogen disposal) as (probably) the two main factors affecting the substrate partition and metabolism

Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

BACKGROUND: In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. METHODS: Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. RESULTS: Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. CONCLUSION: The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood

D'ON VINDRAN LES PROTEÏNES?

Els sistemes alimentaris comprenen tots els elements i totes les activitats relacionades amb la producció, processament, distribució, preparació i consum d'aliments, i també els resultats d'aquestes activitats, incloent-hi també les de tipus socioeconòmic i ambiental. Aquests sistemes estan in tegrats per diverses cadenes de valor i també inclouen activitats que no es tan basades en relacions de mercat, sinó en la cultura, els hàbits socials o l'educació. La principal funció dels sistemes alimentaris és contribuir a la nutrició i la seguretat alimentària de la població, però cada vegada es posa més en relleu el seu paper clau en relació amb la gestió de recursos naturals, la resiliència dels ecosistemes o la mitigació del canvi climàtic, així com en la creació de llocs de treball i la fixació de població al territori. En cap altre àmbit tots aquests elements convergeixen de forma tan explícita i directa

The food energy/protein ratio regulates the rat urea cycle but not total nitrogen losses.

Nitrogen balance studies have shown that a portion of the N ingested but not excreted is not accounted for. We compared several diets (standard, high-fat, high-protein, and self-selected cafeteria) to determine how diet-dependent energy sources affect nitrogen handling, i.e., the liver urea cycle. Diet components and rat homogenates were used for nitrogen, lipid, and energy nalyses. Plasma urea and individual amino acids, as well as liver urea cycle enzyme activities, were determined. Despite ample differences in N intake, circulating amino acids remained practically unchanged in contrast to marked changes in plasma urea. The finding of significant correlations between circulating urea and arginine-succinate synthase and lyase activities supported their regulatory role of urea synthesis, the main N excretion pathway. The cycle operation also correlated with the food protein/energy ratio, in contraposition to total nitrogen losses and estimated balance essentially independent of dietary energy load. The different regulation mechanisms observed have potentially important nutritional consequences, hinting at nitrogen disposal mechanisms able to eliminate excess nitrogen under conditions of high availability of both energy and proteins. Their operation reduces urea synthesis to allow for a safe (albeit unknown) mechanism of N/energy excess accommodation

White adipose tissue urea cycle activity is not affected by one-month treatment with a hyperlipidic diet in female rats.

Under high-energy diets, amino acid N is difficult to dispose of, as a consequence of the availability of alternative substrates. We found, recently, that WAT contains a complete functional urea cycle, we analyzed the possible overall changes in the WAT urea cycle (and other-related amino acid metabolism gene expressions) in rats subjected to a cafeteria diet. Adult female Wistar rats were fed control or simplified cafeteria diets. Samples of WAT sites: mesenteric, periovaric, retroperitoneal and subcutaneous, were used for the estimation of all urea cycle enzyme activities and gene expressions. Other key amino acid metabolism gene expressions, and lactate dehydrogenase were also measured. Subcutaneous WAT showed a differentiated amino acid metabolism profile, since its cumulative (whole site) activity for most enzymes was higher than the activities of the other sites studied. After one month of eating an energy rich cafeteria diet, and in spite of doubling the size of WAT, the transforming capacity of most amino acid metabolism enzymes remained practically unchanged in the tissue. This was not only due to limited changes in the overall enzyme activity, but also a consequence of a relative decrease in the expression of the corresponding genes. Overall, the results of this study support the consideration of WAT as an organ, disperse but under uniform control. The metabolic peculiarities between its different sites, and their ability to adapt to different energy availability conditions only add to the variable nature of adipose tissue. We have presented additional evidence of the significant role of WAT in amino acid metabolism

Stable isotope analysis of dietary arginine accrual and disposal efficiency in male rats fed diets with different protein content.

The administration of diets with different protein/energy ratios induce variable but distinctive responses in rats; an excessive protein content tends to decrease fat accumulation, but reversion of this ratio tends to increase adipose tissue mass. The fate of N derived from amino acid metabolism is not only dependent on energy and dietary protein; the increased excretion of urea elicited by high-protein diets contrasts with the lower urea excretion (despite excess dietary protein and energy) in rats fed a cafeteria diet. After one month of exposure to high-protein (HPD) or cafeteria (CD) diets, we administered a gavage of 15N-arginine to undisturbed adult male rats, in order to trace the utilization of this not-recyclable-N amino acid under diets with different protein/energy relationships. Rats fed high-protein diet excreted higher amounts of N in urine and showed much lower gastrointestinal content of label. The CD rats decreased the excretion of urine N. Both groups' N balance showed a significant proportion of N not-accounted-for (but excreted nevertheless), the proportion being especially large in the HPD group. In conclusion, the process of disposal of amino acid N through the so far unknown pathway for 'non-accounted-for N' is, thus essentially dependent on excess amino acid availability; independently of urea cycle operation and diet energy content

Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

Podeu consultar dades primàries associades a l'article a: http://hdl.handle.net/2445/66872Background and Objectives.White adipose tissue (WAT) shows marked sex- and diet-dependent differences.However, our metabolic knowledge ofWAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four mainWAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent ofWAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesentericWAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males' subcutaneousWAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole

Unconnected body accrual of dietary lipid and protein in rats fed diets with different lipid and protein content

Scope: Eating large amounts of fat is usually associated with fat accumulation. However, different types of diets (not only lipids) elicit different metabolic responses. Methods and results: Male and female rats (10 week-old) are distributed in four groups and fed for 1 month a standard diet (SD), or this diet enriched with either lipid (high-fat diet, HF) or protein (high-protein diet, HP), or a cafeteria diet (CAF). Both HF and CAF diets share the percentage of energy from lipids (40%) but these are different. Protein-derived energy in the HP diet is also 40%. Feeding SD, HF, and HP diets does not result in differences in energy intake, energy expenditure, total body weight, or lipid content. However, the CAF-fed groups show increases in these parameters, which are more marked in the male rats. The CAF diet increases the mass of adipose tissue while the HF diet does not. Conclusion: Different diets produce substantial changes in the fate of ingested nutrient energy. Dietary lipids are not essential for sustaining an increase in body lipid (or adipose tissue) content. Body protein accrual is unrelated to dietary lipids and overall energy intake. Both protein and lipid accrual are more efficient in male rats

Evidences of basal lactate production in the main white adipose tissue sites of rats. Effects of sex and a cafeteria diet.

Female and male adult Wistar rats were fed standard chow or a simplified cafeteria diet for one month. Then, the rats were killed and the white adipose tissue (WAT) in four sites: perigonadal, retroperitoneal, mesenteric and subcutaneous (inguinal) were sampled and frozen. The complete WAT weight in each site was measured. Gene expression analysis of key lipid and glucose metabolism enzymes were analyzed, as well as tissue and plasma lactate and the activity of lactate dehydrogenase. Lactate gradients between WAT and plasma were estimated. The influence of sex and diet (and indirectly WAT mass) on lactate levels and their relationships with lactate dehydrogenase activity and gene expressions were also measured. A main conclusion is the high production of lactate by WAT, practically irrespective of site, diet or sex. Lactate production is a direct correlate of lactate dehydrogenase activity in the tissue. Furthermore, lactate dehydrogenase activity is again directly correlated with the expression of the genes Ldha and Ldhb for this enzyme. In sum, the ability to produce lactate by WAT is not directly dependent of WAT metabolic state.We postulate that, in WAT, a main function of the lactate dehydrogenase path may be that of converting excess available glucose to 3C fragments, as a way to limit tissue self-utilization as substrate, to help control glycaemia and/or providing short chain substrates for use as energy source elsewhere. More information must be gathered before a conclusive role of WAT in the control of glycaemia, and the full existence of a renewed glucose-lactate-fatty acid cycle is definitely established

Modulation of rat liver urea cycle and related ammonium metabolism by sex and cafeteria diet

High-energy (hyperlipidic) cafeteria diets induce insulin resistance limiting glucose oxidation, and lower amino acid catabolism. Despite high amino-N intake, amino acids are preserved, lowering urea excretion. We analysed how energy partition induced by cafeteria diet affects liver ammonium handling and urea cycle. Female and male rats were fed control or cafeteria diets for 30 days. There was a remarkable constancy on enzyme activities and expressions of urea cycle and ammonium metabolism. The key enzymes controlling urea cycle: carbamoyl-P synthase 1, arginino-succinate synthase and arginase expressions were decreased by diet (albeit more markedly in males), and their activities were correlated with the gene expressions. The effects observed, in ammonium handling enzyme activities and expressions behaved in a way similar to that of the urea cycle, showing a generalized downregulation of liver amino acid catabolism. This process was affected by sex. The different strategies of amino-N handling by females and males further modulated the preservation of 2-amino N under sufficient available energy. The effects of sex were more marked than those of diet were, since different metabolism survival strategies changed substrate partition and fate. The data presented suggest a lower than expected N flow to the liver, which overall importance for amino acid metabolism tends to decrease with both cafeteria diet and female sex. Under standard conditions, liver availability of ammonium was low and controlled. The situation was unchanged (or even lowered) in cafeteria-fed rats, ultimately depending on intestinal amino acid catabolism