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

Methods in the treatment of obesity

L'obesitat és una malaltia molt estesa que limita l'activitat i escurça la vida, i que es pot definir com un emmagatzemament patològic de reserves de greix. Malgrat la difusió epidèmica, no hi ha cap sistema plenament efectiu disponible per tractar-la. Les estratègies emprades per al tractament de l'obesitat s'han basat principalment en la l'imitació de la ingesta i/o l'increment de la despesa energètica. EI mètode més emprat per l'imitar la ingesta energètica ha estat la utilització de dietes hipocalòriques, però l'efectivitat és limitada i es perd ràpidament amb el temps. Malgrat això, la utilització adequada de dietes hipocalòriques constitueix encara el principal procediment en la lluita contra el sobrepès. També s'ha emprat el bloqueig de l'absorció de nutrients mitjançant la inhibició específica d'enzims digestius. La cirurgia bariàtrica és ara pràcticament l'únic mètode prou efectiu per tractar els obesos mòrbids. S'ha utilitzat el condicionament conductista per mantenir els obesos allunyats del menjar, però els resultats són sovint poc satisfactoris. No obstant això, la informació adequada que reben els obesos sobre els principis elementals de la nutrició, així com la reeducació nutricional són una eina que no s'ha de deixar de costat. L'exercici és Ia forma més senzilla d'augmentar la despesa energètica i, tot i que aquest increment és sols transitori, potencia els efectes aprimadors de la restricció dietètica. Hi ha un nombre considerable de fàrmacs que han estat emprats per al tractament de l'obesitat i encara n'hi ha més que estan essent estudiats i desenvolupats. EI principal objectiu d'aquests fàrmacs és disminuir la gana a fi d'ajudar l'obès a reduir la quantitat de menjar, però altres drogues tendeixen a incrementar la termogènesi, tot facilitant la utilització de les reserves grasses; sovint ambdós efectes tenen lloc a l'hora. les drogues més àmpliament estudiades són les serotoninèrgiques, que actuen sobre el cervell, i els agents adrenèrgics que aObesity is a widespread crippling and life-shortening disease that can be defined as a pathologic accumulation of fat reserves. In spite of its epidemic distribution, no fully effective treatments are available. The strategies used for the treatment of obesity have relied mainly on the limitation of energy intake or/and increasing energy expenditure. The most widely used method to limit energy intake has been the use of hypocaloric diets. Their effectivity is limited and fade away rapidly with time. Nevertheless, the sound use of hypocaloric diets is yet the mainstay of the fight against overweight. Inhibition of the absorption of nutrients through specific digestive enzyme inhibitors has been also used. Bariatric surgery is now practically the only fairly effective way to treat the morbidly obese. Conductist conditioning has been used to maintain the obese as far as possible from food, but the results are often poor. However, adequate instruction of the obese on basic nutritional knowledge, and nutritional reeducation are a tool not to be neglected. Exercise is the easiest way to increase energy expenditure. but this increase is only transient; in any case it potentiates the slimming effects of dietary restriction. There are a growing number of drugs used for the treatment of obesity, and more are just being under study and development. The main target of these drugs is to diminish the cravings of appetite as a way to help the obese to limit ingestion, but other drugs tend to increase thermogenesis, easing the consumption of fat reserves; often both effects add up. The most widely studied drugs are serotonergic drugs acting on the brain and adrenergic agents acting both on appetite and heat production. Several hormones, metabolites and even poisons have been postulated as antiobesity agents, but now the most promising areas of study rely on hypothalamic control of appetite, thermogenesis and regulatory control of the mass of fat, the latter achieved through signal

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

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

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

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

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

Background: Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results: Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNF¿) values showed overexpression (198%). Conclusion: Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism

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