Biomedical subjects

Charlotte Erlanson-Albertsson

Publications and source records attributed to Charlotte Erlanson-Albertsson.

At least 19 recordsLinked to original sources

PubMed2007

Chloroplast membranes retard fat digestion and induce satiety: effect of biological membranes on pancreatic lipase/co-lipase.

Human obesity is a global epidemic, which causes a rapidly increased frequency of diabetes and cardiovascular disease. One reason for obesity is the ready availability of refined food products with high caloric density, an evolutionarily new event, which makes over-consumption of food inevitable. Fat is a food product with high caloric density. The mechanism for regulation of fat intake has therefore been studied to a great extent. Such studies have shown that, as long as fat stays in the intestine, satiety is promoted. This occurs through the fat-released peptide hormones, the best known being CCK (cholecystokinin), which is released by fatty acids. Hence, retarded fat digestion with prolonged time for delivery of fatty acids promotes satiety. Pancreatic lipase, together with its protein cofactor, co-lipase, is the main enzymatic system responsible for intestinal fat digestion. We found that biological membranes, isolated from plants, animals or bacteria, inhibit the lipase/co-lipase-catalysed hydrolysis of triacylglycerols even in the presence of bile salt. We propose that the inhibition is due to binding of lipase/co-lipase to the membranes and adsorption of the membranes to the aqueous/triacylglycerol interface, thereby hindering lipase/co-lipase from acting on its lipid substrate. We also found that chloroplast membranes (thylakoids), when added to refined food, suppressed food intake in rats, lowered blood lipids and raised the satiety hormones, CCK and enterostatin. Consequently, the mechanism for satiety seems to be retardation of fat digestion allowing the fat products to stay longer in the intestine.

Animals↗

PubMed2006

A putative role for cytokines in the impaired appetite in depression.

Impaired appetite and weight changes are commonly seen in patients with depression, but the pathophysiology behind this imbalance between energy intake and energy expenditure remains largely unknown. The aim of this paper is to review the literature regarding a possible role for cytokines in the regulation of appetite and body weight, with special emphasis on depression. There now exists a substantial amount of evidence that depressed patients show signs of immune activation including increased levels of proinflammatory cytokines. Cytokines, which by themselves have anorectic properties, stimulate the release of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic properties, both proinflammatory cytokines and leptin interact with the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. In turn, these systems regulate energy balance as well as they are dysfunctional in depression. Furthermore, both proinflammatory cytokines and leptin can induce anhedonia, one of the cardinal symptoms of depression. In view of the different effects on appetite and/or body weight observed in melancholic versus atypical depression, we suggest that cytokines are differentially altered in these subtypes of depression, and that this may explain some of the inconsistency in the reported findings of cytokine as well as leptin levels in depressed patients. Finally, we propose that the immune system uses the interoceptive pathway projecting to the insular cortex, a brain region where cytokine-induced changes in appetite could be partly mediated, and that this pathway is activated in depression.

Animals↗

PubMed2006

Appetite suppression through delayed fat digestion.

High-fat diets are often associated with greater caloric intake and weight gain. Since satiety during fat intake is induced by fat in the intestine we investigated the efficiency of a lipid compound that retards fat digestion to regulate fat intake. We found this compound to reduce high-fat food intake, body weight and blood lipids in Sprague-Dawley rats, without causing steatorrhea. The absence of steatorrhea is explained by an increased pancreatic lipase/colipase secretion, compensating the impaired lipolysis by the added compound. The animals also had an elevated CCK secretion. The satiety for fat may be the consequence of elevated CCK and procolipase/enterostatin levels. We conclude that compounds can be found that delay intestinal fat digestion and control high-fat food intake through the release of satiety signals, without causing steatorrhea. The absence of steatorrhea makes such compounds advantageous over lipase inhibitors in the treatment of obesity.

Animals↗

PubMed2005

Overeating of palatable food is associated with blunted leptin and ghrelin responses.

Palatable food is rich in fat and/or sucrose. In this study we examined the long-term effects of such diets on food intake, body weight, adiposity and circulating levels of the satiety peptide leptin and the hunger peptide ghrelin. The experiments involved rats and mice and lasted 5 weeks. In rats, we examined the effect of diets rich in fat and/or sucrose and in mice the effect of a high fat diet with or without sucrose in the drinking water. Animals fed with the palatable diets had a larger intake of calories, gained more weight and became more adipose than animals fed standard rat chow. Fasted animals are known to have low serum leptin and high serum ghrelin and to display elevated serum leptin and lowered serum ghrelin postprandially. With time, a sucrose-rich diet was found to raise the fasting level of leptin and to lower the fasting level of ghrelin in rats. A fat-rich diet suppressed serum ghrelin without affecting serum leptin; high sucrose and high fat in combination greatly reduced serum ghrelin and raised serum leptin in the fasted state. The mRNA expression of leptin in the rat stomach was up-regulated by sucrose-rich (but not by fat-rich) diets, whereas the expression of ghrelin seemed not to be affected by the palatable diets. Mice responded to sucrose in the drinking water with elevated serum leptin (fasted state) and to all palatable diets with low serum ghrelin. The expression of both leptin and ghrelin mRNA in the stomach was suppressed in fasted mice that had received a high fat diet for 5 weeks. We conclude that the expression of leptin mRNA in stomach and the concentration of leptin in serum were elevated in response to sucrose-rich rather than fat-rich diets, linking leptin with sucrose metabolism. In contrast, the expression of ghrelin and the serum ghrelin concentration were suppressed by all palatable diets, sucrose and fat alike. In view of the increased body weight and adiposity neither elevated leptin nor suppressed ghrelin were able to control/restrain the overeating that is associated with palatable diets.

Adipose Tissue↗

PubMed2005

mRNA for pancreatic uncoupling protein 2 increases in two models of acute experimental pancreatitis in rats and mice.

Uncoupling-protein 2 (UCP2) is a mitochondrial protein that appears to be involved in cellular oxidant defense and in the regulation of oncotic cell death, both of which are important features of acute pancreatitis. However, UCP2 expression in acute pancreatitis has not been previously reported. In the current experiments, pancreatic gene expression was studied by real-time reverse-transcription/polymerase chain reaction and Northern blots. Two models of acute experimental pancreatitis were investigated: cerulein-induced pancreatitis in mice at two different time points and taurocholate-induced pancreatitis in rats at two degrees of severity. After cerulein administration, acinar injury and leukocyte infiltration was significantly higher at 24 h compared with 12 h after the first injection of cerulein (P<0.05, P<0.005, respectively). UCP2 mRNA was unchanged at 12 h but was nearly 12-fold greater than control levels after 24 h (P<0.001). UCP2 gene expression correlated with acinar injury (r=0.69; P<0.001). By 72 h after taurocholate administration, the severe group had more necrosis than the mild group (P<0.005). Pancreatic UCP2 mRNA was increased fourfold in the severe group compared with controls (P<0.01). UCP2 expression correlated with parenchymal necrosis (r=0.61; P<0.01). Thus, pancreatic UCP2 mRNA increased in two models of acute pancreatitis. The increase in UCP2 gene expression was correlated with the severity of the disease. Up-regulation of UCP2 in the pancreas may be a protective response to oxidative stress, but this increase may also have a negative influence on cellular energy metabolism. Therefore, acinar UCP2 may be an important modifier of the severity of acute pancreatitis.

Acute Disease↗

PubMed2005

Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure.

Amyloid↗

PubMed2005

The global obesity epidemic: snacking and obesity may start with free meals during infant feeding.

UNLABELLED: Feeding is vital for survival. The brain has strong hunger and reward mechanisms that ensure optimal food intake for adequate nutrition. The drive for feeding is particularly strong in humans whose large brains require large energy support. This starts immediately after birth; the newborn child being able to taste sucrose and suck the sweet and fat from its mother's milk. At present, mothers are generally advised to breastfeed children as often as they like, which may be up to 15 times a day. At the same time, childhood obesity is rapidly developing. One reason for the rapidly increasing prevalence of childhood obesity may be overfeeding with snack food. CONCLUSION: We hypothesize that non-rule breastfeeding favours the development of snacking throughout the day during childhood, a habit which in turn favours the development of obesity.

Appetite Regulation↗

PubMed2005

Appetite regulation and energy balance.

UNLABELLED: The decision to begin eating or to stop eating is a complex process. Hunger is primarily driven by hunger signals, like ghrelin and neuropeptide Y, originating from the gastrointestinal tract and from the hypothalamus. The hunger signals stimulate the seeking of food and the eating, being activating for the body and mind. Thirty minutes after the start of eating, satiety signals arise from the intestinal tract and, in between meals, from the adipose tissue and liver. Satiety signals are sedative and arrest the processing of food in the intestine, hence leading to termination of eating. One problem with overeating today is the ready access to palatable food, such as sucrose and fat. The palatable food works by weakening the satiety signals and activating the hunger signals. The reward system with endogenous opiates may also be activated. CONCLUSIONS: Food and drinks rich in sucrose and fat should be given in a restricted way to children, since there is no biological control feedback to regulate the intake of such products.

Appetite Regulation↗

PubMed2005

How palatable food disrupts appetite regulation.

Appetite regulation is part of a feedback system that controls the energy balance, involving a complex interplay of hunger and satiety signals, produced in the hypothalamus as well as in peripheral organs. Hunger signals may be generated in peripheral organs (e.g. ghrelin) but most of them are expressed in the hypothalamus (neuropeptide Y, orexins, agouti-related peptide, melanin concentrating hormone, endogenous opiates and dopamine) and are expressed during situations of energy deficiency. Some satiety signals, such as cholecystokinin, glucagon-like peptide 1, peptide YY and enterostatin are released from the digestive tract in response to food intake. Others, such as leptin and insulin, are mobilized in response to perturbations in the nutritional state. Still others are generated in neurones of the hypothalamus (alpha-melanocyte-stimulating hormone and serotonin). Satiety signals act by inhibiting the expression of hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in fat and sugar, up-regulates the expression of hunger signals and satiety signals, at the same time blunting the response to satiety signals and activating the reward system. Hence, palatable food offsets normal appetite regulation, which may explain the increasing problem of obesity worldwide.

Animals↗

PubMed2005

Specificity of the 3H-triolein assay for pancreatic lipase in blood plasma.

The aim of this study was to investigate the specificity of the 3H-triolein assay and to investigate the recovery of highly purified pancreatic lipase and pancreatic lipase in the form of pure non-activated pig pancreatic juice. Blood plasma from pigs was analysed for pancreatic lipase activity using the 3H-triolein substrate assay, with a method specific for lipoprotein lipase and with a method specific for hepatic lipase. The recovery of pancreatic lipase from pancreatic juice was approximately 100%, while the recovery of highly purified pancreatic lipase in plasma or whole blood was found to be approximately 1%. Preparations of highly concentrated, purified lipoprotein lipase showed activity in the 3H-triolein assay designed for pancreatic lipase, but the activity did not exceed 1% of the activity of this enzyme measured in an assay specific for lipoprotein lipase (samples containing physiological levels of lipoprotein lipase did not show any activity in the assay). Hepatic lipase was not measurable under the conditions of the 3H-triolein assay. In conclusion, the 3H-triolein assay showed pronounced specificity for pancreatic lipase compared with lipoprotein lipase or hepatic lipase.

Animals↗

PubMed2004

Enterostatin and its target mechanisms during regulation of fat intake.

A high-fat diet easily promotes hyperphagia giving an impression of an uncontrolled process. Fat digestion itself however provides control of fat intake through the digestion itself, carried out by pancreatic lipase and its protein cofactor colipase, and through enterostatin, a peptide released from procolipase during fat digestion. Procolipase (-/-) knockout mice have a severely reduced fat digestion and fat uptake, pointing to a major role of the digestive process itself. With a normal fat digestion, enterostatin basically restricts fat intake by preventing the overconsumption of fat. The mechanism for enterostatin might be an inhibition of a mu-opioid-mediated pathway, demonstrated through binding studies on SK-N-MC-cells and crude brain membranes. Another target protein of enterostatin is the beta-subunit of F1F0-ATPase, displaying a distinct binding of enterostatin, established through an aqueous two-phase partition system. The binding of enterostatin to F1-ATPase was partially displaced by beta-casomorphin, a peptide stimulating fat intake and acting competitively to enterostatin. We frame a hypothesis that regulation of fat intake through enterostatin contains a reward component, which is an F1-ATPase-mediated pathway, possibly complemented with an opioidergic pathway.

Analgesics, Opioid↗

PubMed2004

Decreased UCP2 mRNA expression in rat stomach following vagotomy: novel role for UCP2 as free radical scavenger in the stomach?

Uncoupling protein 2 (UCP2) is a protein, located in the inner mitochondrial membrane, which dissipates the proton gradient of this membrane and uncouples respiration from oxidative phosphorylation. We found, by in situ hybridisation, UCP2 mRNA to be located in the proliferating zone of the mucous neck cells in the fundus part of the rat stomach. We also found that UCP2 expression in fundus was significantly decreased after seven days of vagotomy. Furthermore, we found manganese-containing superoxide dismutase (SOD2), in fundus, to be down-regulated in a way similar to UCP2. The amount of ATP was significantly decreased following vagotomy. It is concluded that UCP2 in the gastro-intestinal tract is regulated through vagal innervation and suggested to act as a free radical scavenger.

Adenosine Diphosphate↗

PubMed2004

The enzyme levels in blood are not affected by oral administration of a pancreatic enzyme preparation (Creon 10,000) in pancreas-insufficient pigs.

After oral intake, small amounts of intact protein may be absorbed into the blood circulation. The current study investigated whether orally administered pancreatic enzymes were absorbed from the intestine. The study included 28 pigs; 3 control pigs with intact pancreatic function and 25 pigs that were made exocrine pancreas insufficient by duct ligation (20 pigs) or total pancreatectomy (5 pigs). The pigs received a pancreatic enzyme preparation (0, 2, 4, or 8 g of Creon 10,000) together with the feed. The blood plasma was analyzed for pancreatic lipase activity with a [3H]-triolein substrate assay, while (pro)colipase and cationic trypsin(ogen) levels were measured with enzyme-linked immunosorbent assay (ELISA). Administration of Creon (0-8 g) caused no significant changes in plasma (pro)colipase or cationic trypsin(ogen) levels. Lipase activity peaks in plasma samples were found, but they did not correspond to the administration of Creon. The potential source of these plasma lipase activity peaks is discussed. The results showed no absorption into blood of pancreatic enzymes after oral administration (0, 2, 4, or 8 g of Creon mixed with 100 g of feed) to pancreas-insufficient pigs.

Administration, Oral↗

PubMed2003

Effect of long-term high-fat feeding on the expression of pancreatic lipases and adipose tissue uncoupling proteins in mice.

INTRODUCTION: A diet containing a high amount of fat has been shown, in short-term studies, to increase the expression of pancreatic lipase and colipase. AIM: To investigate the effects of long-term high-fat-feeding (113 days) on the mRNA expression of pancreatic lipase, colipase, pancreatic lipase-related proteins (1 and 2), and uncoupling proteins during the development of obesity and glucose intolerance. METHODOLOGY: Mice were fed either a high-fat or standard diet and killed after 3, 13, 57, and 113 days. Brown and white adipose tissue and pancreas were collected for mRNA extraction [corrected]. RESULTS: The high-fat-fed mice became obese and glucose-intolerant by 113 days. The high-fat diet increased lipase (p < 0.05) expression initially. At the end of the experiment, the lipase levels had decreased to the level of the control. Colipase levels did not change during the first 57 days of high-fat feeding but decreased below control levels by 113 days (p < 0.05). The high-fat diet increased brown adipose tissue uncoupling protein 1 (UCP1)(p < 0.005) expression but not the expression of uncoupling protein 2. CONCLUSION: Long-term high-fat feeding, leading to glucose intolerance, occurs with a simultaneous decrease in the mRNA expression of pancreatic lipase and colipase and an increase in UCP1 expression.

Adipose Tissue↗

PubMed2002

Plasma enterostatin: identification and release in rats in response to a meal.

OBJECTIVE: To discover a possible absorption and/or secretion of enterostatin into the circulating blood, as well as to compare the levels of circulating enterostatin after high-fat feeding and low-fat feeding. RESEARCH METHODS AND PROCEDURES: Using a specific enzyme-linked immunosorbent assay, plasma enterostatin levels were determined after feeding a high-fat, a high-fat/-sucrose, or a low-fat meal to Sprague-Dawley rats deprived of food overnight. RESULTS: The enterostatin levels were increased by all diets; the response to the high-fat and the high-fat/-sucrose meals was greater in magnitude and duration than that to the low-fat meal. In addition, enterostatin levels correlated with the intake of dietary fat. Plasma enterostatin levels after high-fat feeding were found to be similar to those after intravenous administration of exogenous enterostatin known to inhibit high-fat food intake. Gel chromatography of pooled postprandial plasma extracts followed by high-performance liquid chromatography analysis showed that plasma enterostatin was identical to synthetic enterostatin. Affinity cross-linking of plasma proteins with 125I-enterostatin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography, revealed a single band with a molecular weight of about 66 kDa, indicating the presence of a potential enterostatin-binding protein in plasma. DISCUSSION: The measurements of plasma enterostatin may be a sensitive indicator for the measurement of fat intake.

Animals↗

PubMed2002

Uncoupling proteins--a new family of proteins with unknown function.

Uncoupling proteins are inner mitochondrial membrane proteins, which dissipate the proton gradient, releasing the stored energy as heat. Five proteins have been cloned, named UCP1, UCP2, UCP3, UCP4 and UCP5/BMCP1. These proteins are structurally related but differ in tissue expression. UCP1 is expressed uniquely in the brown adipose tissue, while UCP2 is widely distributed, UCP3 is mainly restricted to skeletal muscle and UCP4 and UCP5/BMCP1 expressed in the brain. The properties and regulation of the uncoupling proteins and their exact function has been the focus of an intense research during recent years. This review briefly summarizes the actual knowledge of the properties and function of this new family of proteins. While UCP1 has a clear role in energy homeostasis, the newcomers UCP2-UCP5 may have more delicate physiological importance acting as free radical oxygen scavengers and in the regulation of ATP-dependent processes, such as secretion.

Animals↗

PubMed2002

Mitochondrial ATP synthase--a possible target protein in the regulation of energy metabolism in vitro and in vivo.

The increasing prevalence of obesity in the Western world has stimulated an intense search for mechanisms regulating food intake and energy balance. A number of appetite-regulating peptides have been identified, their receptors cloned and the intracellular events characterized. One possible energy-dissipating mechanism is the mitochondrial uncoupling of ATP-synthesis from respiratory chain oxidation through uncoupling proteins, whereby energy derived from food could be dissipated as heat, instead of stored as ATP. The exact role of the uncoupling proteins in energy balance is, however, uncertain. We show here that mitochondrial F1F0-ATP synthase itself is a target protein for an anorectic peptide, enterostatin, demonstrated both after affinity purification of rat brain membranes and through a direct physical interaction between enterostatin and purified F1-ATP synthase. In insulinoma cells (INS-1) enterostatin was found to target F1F0-ATP synthase, causing an inhibition of ATP production, an increased thermogenesis and increased oxygen consumption. The experiments suggest a role of mitochondrial F1F0-ATP synthase in the suppressed insulin secretion induced by enterostatin. It could be speculated that this targeting mechanism is involved in the decreased energy efficiency following enterostatin treatment in rat.

Animals↗

PubMed2001

Decreased postnatal survival and altered body weight regulation in procolipase-deficient mice.

In vitro, pancreatic triglyceride lipase requires colipase to restore activity in the presence of inhibitors, like bile acids. Presumably, colipase performs the same function in vivo, but little data supports that notion. Other studies suggest that colipase or its proform, procolipase, may have additional functions in appetite regulation or in fat digestion during the newborn period when pancreatic triglyceride lipase is not expressed. To identify the physiological role of procolipase, we created a mouse model of procolipase deficiency. The Clps-/- mice appeared normal at birth, but unexpectedly 60% died within the first 2 weeks of life. The survivors had fat malabsorption as newborns and as adults, but only when fed a high fat diet. On a low fat diet, the Clps-/- mice did not have steatorrhea. The Clps-/- pups had impaired weight gain and weighed 30% less than Clps+/+ or Clps+/- littermates. After weaning, the Clps-/- mice had normal rate of weight gain, but they maintained a reduced body weight compared with normal littermates even on a low fat diet. Despite the reduced body weight, the Clps-/- mice had a normal body temperature. To maintain their weight gain in the presence of steatorrhea, the Clps-/- mice had hyperphagia on a high fat diet. Clps-/- mice had normal intake on a low fat diet. We conclude that, in addition to its critical role in fat digestion, procolipase has essential functions in postnatal development and in regulating body weight set point.

Age Factors↗