| 31. |
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| 32. |
- Alsiö, Johan, et al.
(författare)
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Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats
- 2014
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 559, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity.
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| 33. |
- Alsiö, Johan, et al.
(författare)
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Feed-forward mechanisms : Addiction-like behavioral and molecular adaptations in overeating
- 2012
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Ingår i: Frontiers in neuroendocrinology (Print). - : Elsevier BV. - 0091-3022 .- 1095-6808. ; 33:2, s. 127-139
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Forskningsöversikt (refereegranskat)abstract
- Food reward, not hunger, is the main driving force behind eating in the modern obesogenic environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences. Important advances have been made to explain mechanisms underlying excessive consumption as an immediate response to presentation of rewarding tastants. However, our understanding of long-term neural adaptations to food reward that oftentimes persist during even a prolonged absence of palatable food and contribute to the reinstatement of compulsive overeating of high-fat high-sugar diets, is much more limited. Here we discuss the evidence from animal and human studies for neural and molecular adaptations in both homeostatic and non-homeostatic appetite regulation that may underlie the formation of a "feed-forward" system, sensitive to palatable food and propelling the individual from a basic preference for palatable diets to food craving and compulsive, addiction-like eating behavior.
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| 34. |
- Alsiö, Johan
(författare)
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From Food Preference to Craving : Behavioural Traits and Molecular Mechanisms
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preference for palatable and energy-dense foods may be a risk factor for body weight gain and has both genetic and environmental components. Once obesity develops in an individual, weight loss is difficult to achieve. Indeed, obesity is often characterized by repeated attempts to reduce the overconsumption of energy-dense foods, followed by food craving and relapse to overconsumption. Relapse and loss of control over intake are observed also in drug addicts, and it has been shown that obesity and drug addiction not only share behavioural features but also neural circuitry, e.g. the mesolimbic dopamine pathway. In this thesis, we sought to investigate the mechanisms related to food preferences and craving using animal models previously used in addiction research. The risk of gaining weight may implicate behavioural traits and emotional states. We showed in rats that a risk-taking behavioural profile was associated both with increased preference for a high-fat (HF) diet and with increased motivational response to a palatable high-sucrose (HS) diet. Hypothalamic urocortin 2 expression was associated with the preference for the HF diet. We also tested the hypothesis that consumption of HS and HF diets separately or provided simultaneously (HFHS) affect anxiety-like behaviour and locomotion. Furthermore, we showed that withdrawal from HFHS food affects diet-induced obesity-prone (OP) and obesity-resistant (OR) animals differently. OP animals had increased motivation (craving) for HS food pellets as measured by the operant self-administration technique during withdrawal. Dopamine receptor expression in the striatum differed between OP and OR animals both at access to HFHS and during withdrawal. This strongly implicates dopaminergic signaling in the OP phenotype. In humans, food preferences may be monitored using questionnaires. We analyzed food preference data from parents of preschool children, and identified an inverse association of parental preference for high-fat high-protein food and overweight in children. In conclusion, we have employed animal models previously used in the addiction field to identify molecular mechanisms related both to food preference and vulnerability to obesity, and to food craving associated with withdrawal from palatable food. These findings add to our current understanding of obesity.
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| 35. |
- Alsiö, Johan, et al.
(författare)
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Impact of nandrolone decanoate on gene expression in endocrine systems related to the adverse effects of anabolic androgenic steroids
- 2009
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 105:5, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- Elite athletes, body builders and adolescents misuse anabolic-androgenic steroids (AAS) in order to increase muscle mass or to enhance physical endurance and braveness. The high doses misused are associated with numerous adverse effects. The purpose of this study was to evaluate the impact of chronic supratherapeutic AAS treatment on circulating hormones and gene expression in peripheral tissues related to such adverse effects. Quantitative real-time PCR was used to measure expression levels of in total 37 genes (including peptide hormones, cell membrane receptors, nuclear receptors, steroid synthesising enzymes and other enzymes) in the pituitary, testes, adrenals, adipose tissue, kidneys and liver of male Sprague-Dawley rats after 14-day administration of the AAS nandrolone decanoate, 3 or 15 mg/kg. Plasma glucose and levels of adrenocorticotropic hormone (ACTH), adiponectin, corticosterone, ghrelin, insulin and leptin were also measured. We found several expected effects on the hypothalamic-pituitary-gonadal axis, while the treatment also caused a number of other not previously identified changes in circulating factors and gene transcription levels such as the dose-dependent reduction of the beta(3)-adrenergic receptor in adipose tissue, reduction of both circulating and mRNA levels of adiponectin, up-regulation of both hydroxymethylglutaryl-CoA-reductase, the rate-limiting enzyme in de novo synthesis of cholesterol, and the receptor for ACTH in the adrenals. The results provide evidence for wide ranging effects of AAS on the hypothalamic-pituitary-adrenal axis, adipose tissue and substrates of the renal control of blood pressure.
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| 36. |
- Alsiö, Johan, et al.
(författare)
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Inverse association of high-fat diet preference and anxiety-like behavior : a putative role for urocortin 2
- 2009
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Ingår i: Genes, Brain and Behavior. - 1601-1848 .- 1601-183X. ; 8:2, s. 193-202
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether the preference for a palatable high-fat diet (HFD) is associated with response to novelty and with anxiety-like behavior in rats and whether such fat preference correlates with gene expression of hypothalamic neuropeptides related to feeding. We subjected male rats to two tests of exploration of novel environments: the multivariate concentric square field (MCSF) and the elevated plus maze (EPM). The rats were then exposed to a 5-day test of preference for a palatable HFD versus reference diets. Messenger RNA (mRNA) levels of 21 neuropeptides were investigated by quantitative polymerase chain reaction. We found a strong positive correlation of HFD preference and open-arm activity in the EPM (% open-arm time, r(s) = 0.629, df = 26, P < 0.001). Thus, HFD preference was inversely associated with anxiety-like behavior. The same association was found for HFD preference and behavior in the MCSF (bridge entries, r(s) = 0.399, df = 23, P = 0.048). In addition, the HFD preference was positively correlated (r(s) = 0.433, df = 25, P = 0.021) with hypothalamic mRNA levels of urocortin 2 (Ucn 2). Moreover, behavior in the EPM was significantly correlated with expression levels of the receptor for Ucn 2, the corticotropin-releasing factor receptor 2, in the hypothalamus (r(s) = 0.382, df = 33, P = 0.022, pituitary (r(s) = 0.494, df = 31, P = 0.004) and amygdala (r(s) = 0.381, df = 30, P = 0.032). We conclude that preference for palatable HFD is inversely associated with anxiety and propose that Ucn 2 signaling may play a role in this association.
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| 37. |
- Alsiö, Johan, et al.
(författare)
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Locomotor adaptation and elevated expression of reward-relevant genes following free-choice high-fat diet exposure
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Obesity may be induced in rodents by long-term access to dietary fat. Such treatment has been reported to have behavioural effects including reduced anxiety-like behaviour and diminished operant responding for psychostimulants. It is unclear whether such effects are secondary to metabolic changes due to excess body weight, or to the extended access to palatable food reward. The aim of this study was to investigate the effects of a short palatable diet exposure (10 days) on performance in the open field test of novelty-induced locomotion and anxiety-like behaviour in rats. We subjected rats to a free-choice high-fat or high-sugar diet, or both, for a period of 10 days. Increased caloric intake was observed in all groups but body weight at Day 10 did not differ from chow-fed controls. We report that consumption of the free-choice high-fat diets was associated with higher novelty-induced activity and reduced anxiety-like behaviour in the open field test. In addition, we used RT-PCR to show that the high-fat group had 39% higher expression of mu opioid receptor in the lateral hypothalamus, and that tyrosine hydroxylase expression was elevated more than two-fold in the ventral tegmental area of rats with access to both high-fat and high-sugar. In conclusion, these results show that subchronic exposure to a free-choice high-fat diet induces behavioural adaptations such as elevated locomotor activity and attenuated experimental anxiety. The changes observed in gene expression related to reward after high-fat diet exposure indicate that these behavioural adaptations are related to reward function.
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| 38. |
- Alsiö, Johan, et al.
(författare)
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Motivation for sucrose in sated rats is predicted by low anxiety-like behavior
- 2009
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Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 454:3, s. 193-197
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Tidskriftsartikel (refereegranskat)abstract
- Anxiety has been implicated in obesity and in the overconsumption of highly palatable foods such as those high in fat, sugar, or both. Also, the novelty-seeking trait has been associated with failure in weight-loss programs. The aim of this study was to investigate the associations of experimental anxiety and the self-administration of sucrose and high fat pellets in non-food deprived rats across different operant schedules. Male Wistar rats were subjected to the elevated plus-maze test (EPM) of anxiety-like behavior. The rats were tested for fixed ratio 5 (FR5) and progressive ratio (PR) operant responding for 50% sucrose, 95% sucrose, and high-fat pellets. PR active lever press response for 95% sucrose, but not the other pellet types, was correlated to % time spent on open arms (P=0.019) in the EPM. On the FR5 schedule, activity (closed arm entries) was correlated to the self-administration of 50% sucrose (P=0.027) and high-fat (P=0.002). This indicates an association of novelty-induced activity and self-administration of palatable food in sated rats, as well as a specific association of PR lever press response for 95% sucrose and low anxiety-like behavior. It has been argued that such active lever press response on PR may be interpreted as craving for the reinforcer; thus, our findings indicate an inverse relationship of experimental anxiety and craving for sucrose. This connection may have implications for human situations, since anxiety and novelty-seeking have been associated with obesity and failure in weight-loss programs.
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| 39. |
- Alsiö, Johan, et al.
(författare)
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Parental food preferences are associated with body weight disturbance in preschool children
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Parental factors such as stress induced by parenting and certain food preferences are suspected to promote obesity in preschool children. In this context, especially the intake of dietary fat is assumed to play a key role for the children’s risk to become obese. Here we analyzed eating behaviors in parents of 3-year-olds in order to identify parental traits that are associated with body weight in these children. We also tested for possible interactions between psychosocial factors such as stress induced by parenting and parental food cravings. Questionnaires were sent out to 1300 parents whose children’s body weight was measured during ambulatory medical care visits (parental response rate 70.4%). Using the Food Craving Inventory scale allowed examining parental preferences for the following food categories: high-fat/high-protein, sweets, carbohydrates, and fast food. Psychosocial stress caused by parenting was assessed with the Swedish Parenthood Stress Questionnaire (SPSQ). Our main finding was that the parental preference for foods rich in high-fat/high-protein nutrients displayed an inverse U-shaped function to the children’s body weight such that low preference for this category was associated with both overweight and underweight in offspring. Parental preference for sweet-foods were associated with higher odds for developing overweight in early childhood. The level of parental food preferences was significantly modulated by stress induced by parenting. In conclusion, we show that parental food preference is affected by stress and is associated with the body weight status of their children. The results suggest that parental intake of high-fat/high-protein foods protects against weight disturbances in preschool children.
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| 40. |
- Andreoli, María F, et al.
(författare)
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Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.
- 2023
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Ingår i: European Journal of Nutrition. - 1436-6207 .- 1436-6215.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations.METHODS: We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB).RESULTS: Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner.CONCLUSIONS: LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans.TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrials.gov (April 2023).CLINICALTRIALS: gov Identifier: NCT05815641.
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