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de Soysa AKH, Langaas M, Grill V, Martins C, Løvold Mostad I. Exploring associations between the FTO rs9939609 genotype and plasma concentrations of appetite-related hormones in adults with obesity. PLoS One 2025; 20:e0312815. [PMID: 39792913 PMCID: PMC11723609 DOI: 10.1371/journal.pone.0312815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 10/14/2024] [Indexed: 01/12/2025] Open
Abstract
Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2. This study explored associations of the rs9939609 genotypes to plasma concentrations of acylated ghrelin, active glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY), and moderating effects of fat mass (FM), in 96 adults (69% female) with BMI ≥35 kg/m2, using a cross sectional observation study designed to have 1/3 of participants each with genotypes TT, AT and AA, respectively. Participants were median (25th, 75th percentile) 42.5 (32, 50) years of age, weighed 120.9 (109.6, 142.4) kg, and had a BMI of 42.8 (39.5, 46.4) kg/m2. Acylated ghrelin, active GLP-1, and total PYY were measured in the fasted state and half-hourly for 2.5h after a standardized meal. We evaluated associations between genotype and appetite hormones in regression analysis controlling for FM and sex. Genotype did not associate with fasting or postprandial (area under curve, AUC) GLP-1 or PYY. Genotype did not associate with fasting acylated ghrelin, but in females with genotype AA, increased FM was associated with higher fasting and postprandial (AUC) acylated ghrelin concentrations relative to genotypes TT (fasting p = 0.025; AUC p = 0.004) and AT (fasting p = 0.002; AUC p < 0.001). This novel finding warrants further investigation.
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Affiliation(s)
- Ann Kristin Hjelle de Soysa
- Outpatient Obesity Clinic, Clinic of Surgery, St. Olavs hospital–Trondheim University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Mette Langaas
- Department of Mathematical Sciences, Faculty of Information Technology and Electrical Engineering, Norwegian University of Science and Technology, Trondheim, Norway
| | - Valdemar Grill
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Catia Martins
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Center for Obesity Research and Innovation (ObeCe), Clinic of Surgery, St. Olavs Hospital–Trondheim University Hospital, Trondheim, Norway
| | - Ingrid Løvold Mostad
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Nutrition and Speech-Language Therapy, Clinic of Rehabilitation, St. Olavs hospital–Trondheim University Hospital, Trondheim, Norway
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de Soysa AKH, Martins C, Langaas M, Grill V, Mostad IL. Exploring Dietary Intake in Adults with Severe Obesity and Associations with the FTO rs9939609 Genotypes. Curr Dev Nutr 2023; 7:100032. [PMID: 37180087 PMCID: PMC10111606 DOI: 10.1016/j.cdnut.2023.100032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/31/2023] Open
Abstract
Background Few have studied the associations between rs9939609 genotypes in the obesity candidate locus FTO and energy and nutrient intakes and meal frequencies in adults with severe obesity. We are unaware of studies that have assessed adherence to key dietary recommendations in this population, at least in Norway. Increased knowledge of genotype associations with dietary factors could improve personalized obesity therapy. Objectives The present study aimed to explore how the rs9939609 genotypes associate with dietary variables and adherence to key dietary recommendations in a sample of adults with severe obesity. Methods A cross-sectional observation study designed to have similar numbers of participants with genotypes TT, AT, and AA included 100 patients (70% women) with median (25th, 75th percentile) age 42 (32, 50) y and BMI 42.8 (39.5, 46.4) kg/m2. We assessed intakes of food groups, energy, and macro- and micronutrients from three 24-h dietary recalls and meal frequencies. Genotype associations were analyzed using regression analyses. Reported intakes were evaluated against national diet recommendations. Results Using a significance level of 0.01, we found no genotype associations with energy intake, energy density, adherence to recommendations, or meal frequency but tendencies of associations with energy adjusted protein intake (AA > AT, P = 0.037; AT > TT, P = 0.064), food groups milk and cream (AT > TT, P = 0.029), and Mixed dishes (AA > TT, P = 0.039). Few participants complied with recommendations for intakes of whole grains (21%), fruits and vegetables (11%), and fish (37%); however, 67% followed the recommendation to limit added sugar. Less than 20% had recommended intakes of vitamin D and folate. Conclusions In our patients with severe obesity, we found tendencies of associations between the FTO rs9939609 genotypes and diet but no significant associations at the 0.01 level and below. Few met key food-based diet recommendations, suggesting that the food habits in this population pose an increased risk of nutrient deficiencies. Curr Dev Nutr 2023;xx:xx.
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Affiliation(s)
- Ann Kristin H. de Soysa
- Department of Clinical Nutrition and Speech-Language Therapy, Clinic of Clinical Services, St. Olavs hospital - Trondheim University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Catia Martins
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Center for Obesity Research and Innovation (ObeCe), Clinic of Surgery, St. Olavs Hospital–Trondheim University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, the University of Alabama at Birmingham, Birmingham, AL, USA
| | - Mette Langaas
- Department of Mathematical Sciences, Faculty of Information Technology and Electrical Engineering, Norwegian University of Science and Technology, Trondheim, Norway
| | - Valdemar Grill
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Ingrid Løvold Mostad
- Department of Clinical Nutrition and Speech-Language Therapy, Clinic of Clinical Services, St. Olavs hospital - Trondheim University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
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Kang Sim DE, Eichen DM, Strong DR, Manzano MA, Boutelle KN. Development and validation of the food cue responsivity scale. Physiol Behav 2023; 258:114028. [PMID: 36368562 PMCID: PMC9754925 DOI: 10.1016/j.physbeh.2022.114028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 11/10/2022]
Abstract
Food cues are ubiquitous in today's environment; however, there is heterogeneity as to the extent to which these cues impact eating behavior among individuals. This study examines the validity and reliability of the Food Cue Responsivity Scale (FCRS) to assess responsivity to distinct types of food cues. Items gathered from existing measures were combined in the FCRS to reflect two subdomains, uncontrolled eating behavior and cognitive rumination. The criterion validity of the FCRS was established using a paradigm that assesses psychophysiological responsivity to a craved food among adults with overweight or obesity. Higher overall FCRS scores were associated with greater physiological responsivity to food exposures. These findings may help identify specific phenotypes of individuals with overweight or obesity with high responsivity to food cues, which could be used to understand overeating and response to weight-loss programs.
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Affiliation(s)
- D Eastern Kang Sim
- Department of Pediatrics, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, United States.
| | - Dawn M Eichen
- Department of Pediatrics, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, United States
| | - David R Strong
- Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego, United States
| | - Michael A Manzano
- Department of Pediatrics, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, United States; San Diego State University/ University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, United States
| | - Kerri N Boutelle
- Department of Pediatrics, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, United States; Herbert Wertheim School of Public Health and Longevity Science, University of California, San Diego, United States; Department of Psychiatry, University of California, San Diego, United States
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Garcia‐Burgos D, Andres F, Trier S, Vögele C, Munsch S. Discrimination of sweet‐fat ingredients in people with weight‐ and eating‐related problems using a signal detection theory. J SENS STUD 2022. [DOI: 10.1111/joss.12783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
| | - Fabienne Andres
- Department of Psychology University of Fribourg Fribourg Switzerland
| | | | - Claus Vögele
- Institute for Health and Behaviour, Department of Behavioural and Cognitive Sciences University of Luxembourg Luxembourg Luxembourg
| | - Simone Munsch
- Department of Psychology University of Fribourg Fribourg Switzerland
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Abstract
The modern obesogenic environment contains an abundance of food cues (e.g., sight, smell of food) as well cues that are associated with food through learning and memory processes. Food cue exposure can lead to food seeking and excessive consumption in otherwise food-sated individuals, and a high level of food cue responsivity is a risk factor for overweight and obesity. Similar food cue responses are observed in experimental rodent models, and these models are therefore useful for mechanistically identifying the neural circuits mediating food cue responsivity. This review draws from both experimental rodent models and human data to characterize the behavioral and biological processes through which food-associated stimuli contribute to overeating and weight gain. Two rodent models are emphasized - cue-potentiated feeding and Pavlovian-instrumental transfer - that provide insight in the neural circuits and peptide systems underlying food cue responsivity. Data from humans are highlighted that reveal physiological, psychological, and neural mechanisms that connect food cue responsivity with overeating and weight gain. The collective literature identifies connections between heightened food cue responsivity and obesity in both rodents and humans, and identifies underlying brain regions (nucleus accumbens, amygdala, orbitofrontal cortex, hippocampus) and endocrine systems (ghrelin) that regulate food cue responsivity in both species. These species similarities are encouraging for the possibility of mechanistic rodent model research and further human research leading to novel treatments for excessive food cue responsivity in humans.
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Affiliation(s)
- Scott E Kanoski
- Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, USA
| | - Kerri N Boutelle
- Department of Pediatrics, Herbert Wertheim School of Public Health and Human Longevity Science, and Psychiatry, University of California San Diego, San Diego, CA, USA.
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Harnischfeger F, O’Connell F, Weiss M, Axelrod B, Hajnal A, Czaja K, Di Lorenzo PM, Dando R. Sprague Dawley Rats Gaining Weight on a High Energy Diet Exhibit Damage to Taste Tissue Even after Return to a Healthy Diet. Nutrients 2021; 13:nu13093062. [PMID: 34578940 PMCID: PMC8465157 DOI: 10.3390/nu13093062] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 12/20/2022] Open
Abstract
Many reports detail taste dysfunction in humans and animals with obesity. For example, mice consuming an obesogenic diet for a short period have fewer taste buds than their lean littermates. Further, rats with diet-induced obesity (DIO) show blunted electrophysiological responses to taste in the brainstem. Here, we studied the effects of high energy diet (HED)-induced peripheral taste damage in rats, and whether this deficiency could be reversed by returning to a regular chow diet. Separate groups of rats consumed a standard chow diet (Chow), a HED for 10 weeks followed by a return to chow (HED/chow), or a HED for 10 weeks followed by a restricted HED that was isocaloric with consumption by the HED/chow group (HED/isocal). Fungiform taste papilla (FP) and circumvallate taste bud abundance were quantified several months after HED groups switched diets. Results showed that both HED/chow and HED/isocal rats had significantly fewer FP and lower CV taste bud abundance than control rats fed only chow. Neutrophil infiltration into taste tissues was also quantified, but did not vary with treatment on this timeline. Finally, the number of cells undergoing programmed cell death, measured with caspase-3 staining, inversely correlated with taste bud counts, suggesting taste buds may be lost to apoptosis as a potential mechanism for the taste dysfunction observed in obesity. Collectively, these data show that DIO has lasting deleterious effects on the peripheral taste system, despite a change from a HED to a healthy diet, underscoring the idea that obesity rather than diet predicts damage to the taste system.
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Affiliation(s)
- Fiona Harnischfeger
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA; (F.H.); (B.A.)
| | - Flynn O’Connell
- Department of Psychology, Binghamton University, Box 6000, Binghamton, NY 13902, USA; (F.O.); (M.W.); (P.M.D.L.)
| | - Michael Weiss
- Department of Psychology, Binghamton University, Box 6000, Binghamton, NY 13902, USA; (F.O.); (M.W.); (P.M.D.L.)
| | - Brandon Axelrod
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA; (F.H.); (B.A.)
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA;
| | - Krzysztof Czaja
- Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA 30602, USA;
| | - Patricia M. Di Lorenzo
- Department of Psychology, Binghamton University, Box 6000, Binghamton, NY 13902, USA; (F.O.); (M.W.); (P.M.D.L.)
| | - Robin Dando
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA; (F.H.); (B.A.)
- Correspondence:
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Obesity-induced taste dysfunction, and its implications for dietary intake. Int J Obes (Lond) 2021; 45:1644-1655. [PMID: 34031530 DOI: 10.1038/s41366-021-00855-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 04/21/2021] [Accepted: 04/30/2021] [Indexed: 02/06/2023]
Abstract
The incidence of obesity has dramatically increased in recent years, and poses a public health challenge for which an effective and scalable intervention strategy is yet to be found. Our food choices are one of the primary drivers of obesity, where the overconsumption of energy from foods high in fat and sugar can be particularly problematic. Unfortunately, these same foods also tend to be highly palatable. We select foods more on their sensory properties than on any other factor, such as price, convenience, or healthfulness. Previous evidence from human sensory studies has suggested a depressed sense of taste in panelists with obesity. Evidence from animal models also demonstrates a clear deficiency in taste buds occurring with obesity, suggesting that damage to the taste system may result from an obese state. In this review only taste, as opposed to smell, will be examined. Here we seek to bring together evidence from a diverse array of human and animal studies into taste response, dietary intake, and physiology, to better understand changes in taste with obesity, with the goal of understanding whether taste may provide a novel target for intervention in the treatment of obesity.
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Children's perceptions of their parent's parenting strategies and child influence on purchases in a supermarket. Appetite 2021; 162:105149. [PMID: 33548351 DOI: 10.1016/j.appet.2021.105149] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 01/31/2021] [Accepted: 02/01/2021] [Indexed: 11/20/2022]
Abstract
This field study identified, through observation, child influence on food and beverage purchases within a supermarket, as well as the influence of the children's perceptions of their parents' parenting strategies related to eating behaviors on these purchases. Four supermarkets were recruited to participate and agreed to allow recruitment of parent-child dyads and implementation of data collection protocols within their stores. Parent-child (7-14 yo) dyads were recruited to wear eye-tracking glasses during the supermarket visit, complete separate individual interviews, and have their store receipts scanned. The receipt data provided evidence of what was purchased, including overall purchases, as well as purchases of energy-dense, nutrient-poor foods and beverages. The eye-tracking data, together with the receipt data, identified which items were requested by the child and purchased. The child interviews provided the child's perceptions of parenting strategies (i.e., parental monitoring, control). Seventy-six dyads agreed to participate and completed the study protocols. During most of the shopping trips, items were purchased as a result of child-initiated request interactions. Children's perceptions of their parent's use of monitoring was consistently associated with fewer purchases overall and of energy-dense, nutrient-poor items, and with reduced child influence on what was purchased.
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van Beurden SB, Greaves CJ, Abraham C, Lawrence NS, Smith JR. ImpulsePal: The systematic development of a smartphone app to manage food temptations using intervention mapping. Digit Health 2021; 7:20552076211057667. [PMID: 34868619 PMCID: PMC8637692 DOI: 10.1177/20552076211057667] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 10/14/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Impulsive processes driving eating behaviour can often undermine peoples' attempts to change their behaviour, lose weight and maintain weight loss. AIM To develop an impulse management intervention to support weight loss in adults. METHODS Intervention Mapping (IM) was used to systematically develop the "ImpulsePal" intervention. The development involved: (1) a needs assessment including a qualitative study, Patient and Public advisory group and expert group consultations, and a systematic review of impulse management techniques; (2) specification of performance objectives, determinants, and change objectives; (3) selection of intervention strategies (mapping of change techniques to the determinants of change); (4) creation of programme materials; (5) specification of adoption and implementation plans; (6) devising an evaluation plan. RESULTS Application of the IM Protocol resulted in a smartphone app that could support reductions in unhealthy (energy dense) food consumption, overeating, and alcoholic and sugary drink consumption. ImpulsePal includes inhibition training, mindfulness techniques, implementation intentions (if-then planning), visuospatial loading, use of physical activity for craving management, and context-specific reminders. An "Emergency Button" was also included to provide access to in-the-moment support when temptation is strong. CONCLUSIONS ImpulsePal is a novel, theory- and evidence-informed, person-centred app that aims to support impulse management for healthier eating. Intervention Mapping facilitated the incorporation of app components that are practical operationalisations of change techniques targeting our specific change objectives and their associated theoretical determinants. Using IM enabled transparency and provided a clear framework for evaluation, and enhances replicability and the potential of the intervention to accomplish the desired outcome of facilitating weight loss through dietary change.
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Affiliation(s)
| | - Colin J Greaves
- School of Sport, Exercise and Rehabilitation, University of Birmingham, Birmingham, UK
| | - Charles Abraham
- School of Psychology, University of Melbourne, Melbourne, AUS
| | | | - Jane R Smith
- College of Medicine of Health, University of Exeter, Exeter, UK
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10
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Appetitive traits as targets for weight loss: The role of food cue responsiveness and satiety responsiveness. Physiol Behav 2020; 224:113018. [PMID: 32562711 DOI: 10.1016/j.physbeh.2020.113018] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 06/05/2020] [Accepted: 06/15/2020] [Indexed: 01/12/2023]
Abstract
Individuals with overweight or obesity (OW/OB) are at increased risk for significant physical and psychological comorbidities. The current treatment for OW/OB is behavioral weight loss, which provides psychoeducation on nutrition and physical activity, as well as behavior therapy skills. However, behavioral weight loss is not effective for the majority of the individuals who participate. Research suggests that overeating, or eating past nutritional needs, is one of the leading causes of weight gain. Accumulating evidence suggests that appetitive traits, such as food cue responsiveness and satiety responsiveness, are associated with overeating and weight in youth and adults. The following review presents the current literature on the relationship between food cue responsiveness, satiety responsiveness, overeating, and OW/OB. Research suggests that higher food cue responsiveness and lower satiety responsiveness are associated with overeating and OW/OB cross-sectionally and longitudinally. Emerging data suggest that food cue responsiveness and satiety responsiveness may exist along the same continuum and can be targeted to manage overeating and reduce weight. We have developed a treatment model targeting food cue responsiveness and satiety responsiveness to reduce overeating and weight and have preliminary feasibility, acceptability, and efficacy data, with testing currently being conducted in larger trials. Through programs targeting appetitive traits we hope to develop an alternative weight loss model to assist individuals with a propensity to overeat.
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McLean FH, Campbell FM, Langston RF, Sergi D, Resch C, Grant C, Morris AC, Mayer CD, Williams LM. A high-fat diet induces rapid changes in the mouse hypothalamic proteome. Nutr Metab (Lond) 2019; 16:26. [PMID: 31168311 PMCID: PMC6489262 DOI: 10.1186/s12986-019-0352-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 04/12/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Prolonged over-consumption of a high-fat diet (HFD) commonly leads to obesity and insulin resistance. However, even 3 days of HFD consumption has been linked to inflammation within the key homeostatic brain region, the hypothalamus. METHODS Mice were fed either a low-fat diet (LFD) or HFD containing 10% or 60% (Kcal) respectively from fat for 3 days. Mice were weighed, food intake measured and glucose tolerance calculated using intraperitoneal glucose tolerance tests (IPGTT). Proteomic analysis was carried out to determine if hypothalamic proteins were changed by a HFD. The direct effects of dietary fatty acids on mitochondrial morphology and on one of the proteins most changed by a HFD, dihydropyrimidinase-related protein 2 (DRP-2) a microtubule-associated protein which regulates microtubule dynamics, were also tested in mHypoE-N42 (N42) neuronal cells challenged with palmitic acid (PA) and oleic acid (OA). RESULTS Mice on the HFD, as expected, showed increased adiposity and glucose intolerance. Hypothalamic proteomic analysis revealed changes in 104 spots after 3 days on HFD, which, when identified by LC/MS/MS, were found to represent 78 proteins mainly associated with cytoskeleton and synaptic plasticity, stress response, glucose metabolism and mitochondrial function. Over half of the changed proteins have also been reported to be changed in neurodegenerative conditions such as Alzheimer's disease. Also,in N42 neurons mitochondrial morphology and DRP-2 levels were altered by PA but not by OA. CONCLUSION These results demonstrate that within 3 days, there is a relatively large effect of HFD on the hypothalamic proteome indicative of cellular stress, altered synaptic plasticity and mitochondrial function, but not inflammation. Changes in N42 cells show an effect of PA but not OA on DRP-2 and on mitochondrial morphology indicating that long-chain saturated fatty acids damage neuronal function.
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Affiliation(s)
- Fiona H. McLean
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
- Division of Neuroscience, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY UK
| | - Fiona M. Campbell
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
| | - Rosamund F. Langston
- Division of Neuroscience, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY UK
| | - Domenico Sergi
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
- Nutrition & Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA 5000 Australia
| | - Cibell Resch
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
| | - Christine Grant
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
| | - Amanda C. Morris
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
| | - Claus D. Mayer
- Biomathematics and Statistics Scotland, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Lynda M. Williams
- Rowett Institute, University of Aberdeen Foresterhill Campus, Aberdeen, AB25 2ZD UK
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Sergi D, Campbell FM, Grant C, Morris AC, Bachmair EM, Koch C, McLean FH, Muller A, Hoggard N, de Roos B, Porteiro B, Boekschoten MV, McGillicuddy FC, Kahn D, Nicol P, Benzler J, Mayer CD, Drew JE, Roche HM, Muller M, Nogueiras R, Dieguez C, Tups A, Williams LM. SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice. GENES AND NUTRITION 2018; 13:28. [PMID: 30519364 PMCID: PMC6263559 DOI: 10.1186/s12263-018-0619-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 11/06/2018] [Indexed: 02/08/2023]
Abstract
Background Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus. Results Mouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1−/−) mice. Conclusions These data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation.
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Affiliation(s)
- Domenico Sergi
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Fiona M Campbell
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Christine Grant
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Amanda C Morris
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | | | - Christiane Koch
- 2Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch Str. 8, 35043 Marburg, Germany.,3Centre for Neuroendocrinology and Brain Health Research Centre, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, 9054 New Zealand
| | - Fiona H McLean
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Aifric Muller
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Nigel Hoggard
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Baukje de Roos
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Begona Porteiro
- 4Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain.,5CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain
| | - Mark V Boekschoten
- 6Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
| | - Fiona C McGillicuddy
- 7Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Darcy Kahn
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Phyllis Nicol
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Jonas Benzler
- 2Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch Str. 8, 35043 Marburg, Germany.,3Centre for Neuroendocrinology and Brain Health Research Centre, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, 9054 New Zealand
| | - Claus-Dieter Mayer
- 8Biomathematics & Statistics Scotland (BioSS), Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Janice E Drew
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Helen M Roche
- 7Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Michael Muller
- 9Nutrigenomics and Systems Nutrition Group, Norwich Medical School, University of East Anglia, Norwich, NR4 7UQ UK
| | - Ruben Nogueiras
- 4Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain.,5CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain
| | - Carlos Dieguez
- 4Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain.,5CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain
| | - Alexander Tups
- 2Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch Str. 8, 35043 Marburg, Germany.,3Centre for Neuroendocrinology and Brain Health Research Centre, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, 9054 New Zealand
| | - Lynda M Williams
- 1Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD UK
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13
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Zhang XY, Shen W, Liu DZ, Wang DH. Diversity of Thermogenic Capacity Predicts Divergent Obesity Susceptibility in a Wild Rodent. Obesity (Silver Spring) 2018; 26:111-118. [PMID: 29131548 DOI: 10.1002/oby.22055] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 09/25/2017] [Accepted: 09/28/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The objective of the present study was to examine whether wild rodents exhibit diverse obesity susceptibility and what factors predispose subjects to this divergence in response to a high-fat diet (HFD). METHODS Sixty male and female Brandt's voles (Lasiopodomys brandtii) were fed an HFD for 8 weeks, and the upper (obesity prone [OP]) and lower (obesity resistant [OR]) one-third for mass gain were selected. Energy budgets and pathologic changes were measured. Another 30 males were fed a low-fat control diet (LFD) for 10 weeks and then fed an HFD for 12 weeks. The energetic parameters of the rodents on an LFD were analyzed for the correlation with body mass of the rodents on an HFD. RESULTS OP voles had higher energy intakes, higher levels of noradrenaline-induced nonshivering thermogenesis, and a greater impairment of insulin tolerance than OR voles. Unlike laboratory rodents, there were no differences in physical activity or resting metabolic rate between these groups of voles. The thermogenic capacity during LFD feeding was the strongest predictor for mass gain during HFD feeding. CONCLUSIONS This study suggests that a wild rodent species of Brandt's voles exhibits diverse obesity susceptibility in reaction to an HFD, providing a natural model to give insight into the mechanisms for divergent obesity susceptibility. This study also indicates that maximum thermogenic capacity has a predictive power for the development of obesity when an HFD was available.
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Affiliation(s)
- Xue-Ying Zhang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Wei Shen
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Key Laboratory of Biodiversity Science and Ecological Engineering of the Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China
| | - Ding-Zhen Liu
- Key Laboratory of Biodiversity Science and Ecological Engineering of the Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China
| | - De-Hua Wang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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14
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Chen Z, Zhao H, Fu N, Chen L. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues. J Cell Physiol 2017; 233:2104-2115. [PMID: 28338216 DOI: 10.1002/jcp.25929] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 03/22/2017] [Indexed: 12/28/2022]
Abstract
Olfactory receptors (ORs) are mainly distributed in olfactory neurons and play a key role in detecting volatile odorants, eventually resulting in the production of smell perception. Recently, it is also reported that ORs are expressed in non-olfactory tissues including heart, lung, sperm, skin, and cancerous tissues. Interestingly, ectopic ORs are associated with the development of diseases in non-olfactory tissues. For instance, ectopic ORs initiate the hypoxic ventilatory responses and maintain the oxygen homeostasis of breathing in the carotid body when oxygen levels decline. Ectopic ORs induce glucose homeostasis in diabetes. Ectopic ORs regulate systemic blood pressure by increasing renin secretion and vasodilation. Ectopic ORs participate in the process of tumor cell proliferation, apoptosis, metastasis, and invasiveness. Ectopic ORs accelerate the occurrence of obesity, angiogenesis and wound-healing processes. Ectopic ORs affect fetal hemoglobin levels in sickle cell anemia and thalassemia. Finally, we also elaborate some ligands targeting for ORs. Obviously, the diversified function and related signal pathway of ectopic ORs may play a potential therapeutic target in non-olfactory tissues. Thus, this review focuses on the latest research results about the diversified function and therapeutic potential of ectopic ORs in non-olfactory tissues.
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Affiliation(s)
- Zhe Chen
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
| | - Hong Zhao
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
| | - Nian Fu
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
| | - Linxi Chen
- Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China
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15
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Lucas-Thompson RG, Graham DJ, Ullrich E, MacPhee D. General and food-selection specific parenting style in relation to the healthfulness of parent-child choices while grocery shopping. Appetite 2017; 108:353-360. [DOI: 10.1016/j.appet.2016.10.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 08/22/2016] [Accepted: 10/14/2016] [Indexed: 10/20/2022]
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16
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Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiol Rev 2017; 97:411-463. [PMID: 28003328 PMCID: PMC6151490 DOI: 10.1152/physrev.00031.2014] [Citation(s) in RCA: 402] [Impact Index Per Article: 50.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.
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Affiliation(s)
- Robert E Steinert
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Christine Feinle-Bisset
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Lori Asarian
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Michael Horowitz
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Christoph Beglinger
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Nori Geary
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
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17
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Estimating the impact of various menu labeling formats on parents’ demand for fast-food kids’ meals for their children: An experimental auction. Appetite 2016; 105:582-90. [DOI: 10.1016/j.appet.2016.06.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Revised: 05/18/2016] [Accepted: 06/13/2016] [Indexed: 01/06/2023]
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18
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Weight Gain Prevention among Midlife Women: A Randomized Controlled Trial to Address Needs Related to the Physical and Social Environment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:ijerph13060530. [PMID: 27231927 PMCID: PMC4923987 DOI: 10.3390/ijerph13060530] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 05/19/2016] [Accepted: 05/20/2016] [Indexed: 11/17/2022]
Abstract
Women tend to gain weight at midlife (40–60 years) increasing risk of obesity-related chronic diseases. Within specific eating occasions, needs related to the physical and social environment may result in less healthy eating behavior, which can lead to weight gain over time. The purpose of this study was to determine if a dietitian-delivered nutrition counseling intervention tailored to eating occasion needs could improve diet and prevent weight gain among midlife women over two years. A randomized controlled trial was conducted with healthy midlife women (n = 354) in one U.S. metropolitan area. The intervention group (n = 185) received ten hours of individual nutrition counseling from dietitians over six months, while women in a control group (n = 169) received no counseling. Measured height, weight and waist circumference, and dietary intakes were collected at baseline and every six months over two years. Mixed linear models were used to test for intervention effect on change in outcome variables over time. Dietary intakes of fruit, reduced/low-fat dairy foods and refined grains were significantly improved over time in the intervention compared to control group. However, the intervention had no effect on weight over time (p = 0.48). Nutrition counseling tailored to address eating occasion needs improved self-reported diet but did not significantly affect weight change.
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19
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Boutelle KN, Bouton ME. Implications of learning theory for developing programs to decrease overeating. Appetite 2015; 93:62-74. [PMID: 25998235 PMCID: PMC4654402 DOI: 10.1016/j.appet.2015.05.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 04/30/2015] [Accepted: 05/12/2015] [Indexed: 01/09/2023]
Abstract
Childhood obesity is associated with medical and psychological comorbidities, and interventions targeting overeating could be pragmatic and have a significant impact on weight. Calorically dense foods are easily available, variable, and tasty which allows for effective opportunities to learn to associate behaviors and cues in the environment with food through fundamental conditioning processes, resulting in measurable psychological and physiological food cue reactivity in vulnerable children. Basic research suggests that initial learning is difficult to erase, and that it is vulnerable to a number of phenomena that will allow the original learning to re-emerge after it is suppressed or replaced. These processes may help explain why it may be difficult to change food cue reactivity and overeating over the long term. Extinction theory may be used to develop effective cue-exposure treatments to decrease food cue reactivity through inhibitory learning, although these processes are complex and require an integral understanding of the theory and individual differences. Additionally, learning theory can be used to develop other interventions that may prove to be useful. Through an integration of learning theory, basic and translational research, it may be possible to develop interventions that can decrease the urges to overeat, and improve the weight status of children.
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Affiliation(s)
- Kerri N Boutelle
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
| | - Mark E Bouton
- Department of Psychological Science, University of Vermont, Burlington, VT, USA
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20
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Higuera-de la Tijera F, Servín-Caamaño AI. Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets. World J Hepatol 2015; 7:1297-1301. [PMID: 26052375 PMCID: PMC4450193 DOI: 10.4254/wjh.v7.i10.1297] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 02/21/2015] [Accepted: 03/16/2015] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health care problem and represents the hepatic expression of the metabolic syndrome. NAFLD is classified as non-alcoholic fatty liver (NAFL) or simple steatosis, and non-alcoholic steatohepatitis (NASH). NASH is characterized by the presence of steatosis and inflammation with or without fibrosis. The physiopathology of NAFL and NASH and their progression to cirrhosis involve several parallel and interrelated mechanisms, such as, insulin resistance (IR), lipotoxicity, inflammation, oxidative stress, and recently the gut-liver axis interaction has been described. Incretin-based therapies could play a role in the treatment of NAFLD. Glucagon-like peptide-1 (GLP-1) is an intestinal mucosa-derived hormone which is secreted into the bloodstream in response to nutrient ingestion; it favors glucose-stimulated insulin secretion, inhibition of postprandial glucagon secretion and delayed gastric emptying. It also promotes weight loss and is involved in lipid metabolism. Once secreted, GLP-1 is quickly degraded by dipeptidyl peptidase-4 (DPP-4). Therefore, DPP-4 inhibitors are able to extend the activity of GLP-1. Currently, GLP-1 agonists and DPP-4 inhibitors represent attractive options for the treatment of NAFLD and NASH. The modulation of lipid and glucose metabolism through nuclear receptors, such as the farsenoid X receptor, also constitutes an attractive therapeutic target. Obeticholic acid is a potent activator of the farnesoid X nuclear receptor and reduces liver fat content and fibrosis in animal models. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with immunomodulatory, anti-inflammatory, antiapoptotic, antioxidant and anti-fibrotic properties. UDCA can improve IR and modulate lipid metabolism through its interaction with nuclear receptors such as, TGR5, farnesoid X receptor-α, or the small heterodimeric partner. Finally, pharmacologic modulation of the gut microbiota could have a role in the therapy of NAFLD and NASH. Probiotics prevent bacterial translocation and epithelial invasion, inhibit mucosal adherence by bacteria, and stimulate host immunity. In animal models, probiotics prevent obesity, decrease transaminase levels, and improve IR and liver histology in NASH.
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Affiliation(s)
- Fátima Higuera-de la Tijera
- Fátima Higuera-de la Tijera, Liver Clinic, Gastroenterology Department, Mexico's General Hospital "Dr. Eduardo Liceaga", Mexico City 06726, Mexico
| | - Alfredo I Servín-Caamaño
- Fátima Higuera-de la Tijera, Liver Clinic, Gastroenterology Department, Mexico's General Hospital "Dr. Eduardo Liceaga", Mexico City 06726, Mexico
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21
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The effects of calorie labels on those at high-risk of eating pathologies: a pre-post intervention study in a University cafeteria. Public Health 2015; 129:732-9. [PMID: 25931435 DOI: 10.1016/j.puhe.2015.03.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Revised: 02/23/2015] [Accepted: 03/07/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The aim of the study was to examine the effect of a public policy (menu labelling) on those at high-risk for eating pathologies. Specifically, the study looked for any adverse effects related to eating disturbance level. STUDY DESIGN The study employed a pre-post intervention design. Baseline collection took place in October 2012. One week prior to follow-up in November 2012, calorie labels were displayed next to virtually all menu items in a University cafeteria. Labels remained throughout the entire duration of follow-up. METHODS Participants were female undergraduates (N = 299). At baseline and follow-up, a survey assessed eating disturbance level (Eating Attitudes Test-26), emotional state, frequency of engaging in unhealthy weight-related behaviours, and calorie consumption. RESULTS Generalized estimating equations were used to test changes in negative outcomes over time in response to calorie labels. Calorie consumption did not significantly decrease from baseline (mean = 660.5 kcal) to follow-up (mean = 600.5 kcal; P = 0.104). There were no changes in emotional states such as body image satisfaction (P = 0.447), anxiety (P = 0.595), positive affect (P = 0.966), negative affect (P = 0.576), and unhealthy weight-related behaviours such as binging (P = 0.268), exercising excessively (P = 0.847), or restricting calories (P = 0.504). Additionally, there were no interactions between eating disturbance level and time. CONCLUSIONS Overall, no adverse outcomes were found for this at-risk population. Calorie labels did not differentially affect those with higher levels of eating disturbance. Future research should focus on examining the impact of calorie labels among those with clinical eating disorders.
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22
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Xu X, Variyam JN, Zhao Z, Chaloupka FJ. Relative food prices and obesity in US Metropolitan areas: 1976-2001. PLoS One 2014; 9:e114707. [PMID: 25502888 PMCID: PMC4264774 DOI: 10.1371/journal.pone.0114707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 11/12/2014] [Indexed: 02/02/2023] Open
Abstract
This study investigates the impact of food price on obesity, by exploring the co-occurrence of obesity growth with relative food price reduction between 1976 and 2001. Analyses control for female labor participation and metropolitan outlet densities that might affect body weight. Both the first-difference and fixed effects approaches provide consistent evidence suggesting that relative food prices have substantial impacts on obesity and such impacts were more pronounced among the low-educated. These findings imply that relative food price reductions during the time period could plausibly explain about 18% of the increase in obesity among the U.S. adults in metropolitan areas.
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Affiliation(s)
- Xin Xu
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois, United States of America
| | - Jayachandran N Variyam
- Food Economics Division, Economic Research Service, U. S. Department of Agriculture, Washington, District of Columbia, United States of America
| | - Zhenxiang Zhao
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois, United States of America
| | - Frank J Chaloupka
- Institute for Health Research and Policy, Department of Economics, University of Illinois at Chicago, National Bureau of Economic Research, Chicago, Illinois, United States of America
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23
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Dahl U, Rise MB, Kulseng B, Steinsbekk A. Personnel and participant experiences of a residential weight-loss program. A qualitative study. PLoS One 2014; 9:e100226. [PMID: 24937479 PMCID: PMC4061127 DOI: 10.1371/journal.pone.0100226] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 05/24/2014] [Indexed: 11/19/2022] Open
Abstract
Background Residential weight-loss programs aim to help persons with obesity lose weight and maintain a long-term healthy lifestyle. Knowledge is needed on the different actors’ perceptions and experiences from such programs. The aim of this study was to describe how personnel argued for and perceived a residential weight-loss program, to investigate how the participants experienced the program, and to contrast these perspectives. Methods This qualitative study took place in an 18-week residential weight-loss program. Exercise, diet, and personal development were the main components in the program. Data was collected through participant observation and individual and focus group interviews with participants and personnel. Results Program personnel characterized persons with obesity in specific terms, and these formed the basis of the educational aims, teaching principles, and content of the program. According to personnel, persons with obesity typically had problems acknowledging their own resources, lived unstructured lives, had a distorted relationship to food, experienced a range of social problems and featured a lack of personal insight. Program participants reported enthusiasm about their experiences of exercise and appreciated measures of success with the exercise program. They had, however, very different experiences regarding the usefulness and appropriateness of the parts of the program focused on social and personal development. Some felt that weight loss required an engagement with personal development while others viewed it as unnecessary and inappropriate. Conclusion The reliance in personnel accounts on particular characteristics of persons with obesity as a rationale for the program might lead to stigmatizing and stereotyping. Program activities focused on social and personal development need to be better understood by participants if they are to be viewed as helpful. To achieve this personnel must carefully consider how these parts of the program are communicated and conducted.
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Affiliation(s)
- Unni Dahl
- Central Norway Health Authority, Stjørdal, Norway
- Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
| | - Marit By Rise
- Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
- * E-mail:
| | - Bård Kulseng
- Regional Centre for Obesity Treatment, St. Olav’s University Hospital, Trondheim, Norway
| | - Aslak Steinsbekk
- Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
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24
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Li J, O'Connor LE, Zhou J, Campbell WW. Exercise patterns, ingestive behaviors, and energy balance. Physiol Behav 2014; 134:70-5. [PMID: 24747277 DOI: 10.1016/j.physbeh.2014.04.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Revised: 04/07/2014] [Accepted: 04/08/2014] [Indexed: 01/29/2023]
Abstract
Ingestive and exercise behaviors are important determinants of whole body energy balance and weight control. An acute bout of exercise generates a transient energy deficit, which is only partially compensated for by food intake at the next eating occasion or within the next day (loose dietary coupling). Such an energy deficit, when repeated chronically, leads to moderate weight loss and improved body composition. For this narrative review, we assessed the effects of exercise patterns on energy intake, energy balance, and weight control in adults primarily using results from randomized acute exercise and chronic training studies. The patterns assessed were exercise mode (e.g. resistance, aerobic exercise), intensity, duration, time of day, and frequency. The body of evidence indicates that exercise training frequency and quantity are influential for weight loss. Aerobic training is superior to resistance training for weight loss, although resistance training helps preserve lean body mass better. Weight loss does not differ among different intensities when energy expenditure is matched by adjusting duration. Differing patterns of physical activity exhibited by normal weight, overweight, and obese people during weekdays and weekend days are consistent with their weight status; leaner people are more physically active. Collectively, these findings support acute and chronic exercise patterns as important modifiable behaviors to improve energy balance and weight control in adults while having minor effects on absolute energy intake.
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Affiliation(s)
- Jia Li
- Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.
| | - Lauren E O'Connor
- Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.
| | - Jing Zhou
- Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.
| | - Wayne W Campbell
- Department of Nutrition Science, Purdue University, 700 W. State Street, West Lafayette, IN 47907, USA.
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25
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DiSantis KI, Grier SA, Oakes JM, Kumanyika SK. Food prices and food shopping decisions of black women. Appetite 2014; 77:104-12. [PMID: 24583415 DOI: 10.1016/j.appet.2014.02.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 02/02/2014] [Accepted: 02/24/2014] [Indexed: 11/29/2022]
Abstract
Identifying food pricing strategies to encourage purchases of lower-calorie food products may be particularly important for black Americans. Black children and adults have higher than average obesity prevalence and disproportionate exposure to food marketing environments in which high calorie foods are readily available and heavily promoted. The main objective of this study was to characterize effects of price on food purchases of black female household shoppers in conjunction with other key decision attributes (calorie content/healthfulness, package size, and convenience). Factorial discrete choice experiments were conducted with 65 low- and middle-/higher-income black women. The within-subject study design assessed responses to hypothetical scenarios for purchasing frozen vegetables, bread, chips, soda, fruit drinks, chicken, and cheese. Linear models were used to estimate the effects of price, calorie level (or healthfulness for bread), package size, and convenience on the propensity to purchase items. Moderating effects of demographic and personal characteristics were assessed. Compared with a price that was 35% lower, the regular price was associated with a lesser propensity to purchase foods in all categories (β = -0.33 to -0.82 points on a 1 to 5 scale). Other attributes, primarily calorie content/healthfulness, were more influential than price for four of seven foods. The moderating variable most often associated with propensity to pay the regular versus lower price was the reported use of nutrition labels. Price reductions alone may increase purchases of certain lower-calorie or more healthful foods by black female shoppers. In other cases, effects may depend on combining price changes with nutrition education or improvements in other valued attributes.
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Affiliation(s)
- Katherine I DiSantis
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, 8th Floor Blockley Hall, Philadelphia, PA 19104, USA
| | - Sonya A Grier
- Department of Marketing, Kogod School of Business, American University, 4400 Massachusetts Avenue, NW, Washington, DC, WA 20016-8044, USA
| | - J Michael Oakes
- Division of Epidemiology, University of Minnesota School of Public Health, West Bank Office Building, 1300 S. Second Street, Suite 300, Minneapolis, MN 55454-1015, USA
| | - Shiriki K Kumanyika
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, 8th Floor Blockley Hall, Philadelphia, PA 19104, USA.
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Abstract
BACKGROUND Food consumed outside the home accounts for a growing proportion of the North American diet and has been associated with increased obesity. PURPOSE To examine the effect of nutrition labeling on menus on awareness, use, and food consumption, including the impact of "traffic light" labeling and adding other nutrients. METHODS Blinded, randomized trial with 635 Canadian adults conducted in 2010-2011. Participants ordered a free meal from one of four experimental menus: 1) no nutritional information shown, 2) calorie amounts only, 3) calorie amounts in "traffic lights", and 4) calorie, fat, sodium, and sugar shown in "traffic lights". Recall of nutrition information, knowledge of calorie content and nutrient consumption were assessed. RESULTS Participants in the calorie conditions were more likely to recall the calorie content of meals and to report using nutrition information when ordering. The calorie content of meals was not significantly different across conditions; however, calorie consumption was significantly lower among participants in the Calorie-only condition compared to the No information condition (mean=-96 kcal, p=.048). CONCLUSIONS Menu labeling increased awareness and use of nutrition information and reduced consumption. Adding "traffic lights", fat, sodium, and sugar amounts to menus had little impact compared to calorie-only labeling.
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Appelhans BM, Bleil ME, Waring ME, Schneider KL, Nackers LM, Busch AM, Whited MC, Pagoto SL. Beverages contribute extra calories to meals and daily energy intake in overweight and obese women. Physiol Behav 2013; 122:129-33. [PMID: 24041722 PMCID: PMC3840121 DOI: 10.1016/j.physbeh.2013.09.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 09/03/2013] [Accepted: 09/07/2013] [Indexed: 11/13/2022]
Abstract
Caloric beverages may promote obesity by yielding energy without producing satiety, but prior laboratory and intervention studies are inconclusive. This study examined whether the diets of free-living overweight and obese women show evidence that calories from beverages are offset by reductions in solid food within individual eating occasions and across entire days. Eighty-two women weighed and recorded all consumed foods and beverages for seven days. Beverages were coded as high-calorie (≥ 0.165 kcal/g) or low-calorie (<0.165 kcal/g), and total energy intake and energy intake from solid food were calculated for each eating occasion and day. In covariate-adjusted models, energy intake from solid food did not differ between eating occasions that included high-calorie or low-calorie beverages and those with no reported beverage. Energy intake from solid food was also unrelated to the number of high-calorie or low-calorie beverages consumed per day. On average, eating occasions that included a high-calorie beverage were 169 kcal higher in total energy than those with no reported beverage, and 195 kcal higher in total energy than those that included a low-calorie beverage. Each high-calorie beverage consumed per day contributed an additional 147 kcal to women's daily energy intake, whereas low-calorie beverage intake was unrelated to daily energy intake. Beverages contributed to total energy intake in a near-additive fashion among free-living overweight and obese women, suggesting a need to develop more effective interventions to reduce caloric beverage intake in the context of weight management, and to potentially reexamine dietary guidelines.
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Affiliation(s)
- Bradley M Appelhans
- Department of Preventive Medicine, Rush University Medical Center, 1700 W. Van Buren St., Suite 470, Chicago, IL 60612, United States.
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Heinonen I, Helajärvi H, Pahkala K, Heinonen OJ, Hirvensalo M, Pälve K, Tammelin T, Yang X, Juonala M, Mikkilä V, Kähönen M, Lehtimäki T, Viikari J, Raitakari OT. Sedentary behaviours and obesity in adults: the Cardiovascular Risk in Young Finns Study. BMJ Open 2013; 3:bmjopen-2013-002901. [PMID: 23794543 PMCID: PMC3669715 DOI: 10.1136/bmjopen-2013-002901] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Sedentary behaviour may contribute to the development of obesity. We investigated the relations between different types of sedentary behaviour and adiposity markers in a well-characterised adult population after controlling for a wide range of potential confounders. DESIGN Cross-sectional study. SETTING The Cardiovascular Risk in Young Finns Multicenter Study. Participants Sedentary time (TV viewing, computer time, reading, music/radio listening and other relaxation) was assessed with a questionnaire for 1084 women and 909 men aged 30-45 years. Other study variables included occupational and leisure-time physical activity, sleep duration, socioeconomic status, smoking, alcohol consumption, energy intake, adherence to the recommended diet, multiple individual food items, age and genetic variants associated with body mass index (BMI). Primary outcome measures BMI in kg/m(2) and waist circumference (WC in cm). RESULTS Of the different sedentary behaviour types, TV viewing was most consistently related to higher BMI and WC, both in men and women. One additional daily TV hour was associated with a 1.81±0.44 cm larger WC in women and 2 cm±0.44 cm in men (both p<0.0001). The association with TV was diluted, but remained highly significant after adjustments with all measured covariates, including several potentially obesogenic food items associated with TV viewing. The intakes of food items such as sausage, beer and soft drinks were directly associated with TV viewing, while the intakes of oat and barley, fish, and fruits and berries were associated indirectly. After these adjustments, non-TV sedentary behaviour remained associated with adiposity indices only in women. CONCLUSIONS Out of the different types of sedentary behaviour, TV viewing was most consistently associated with adiposity markers in adults. Partial dilution of these associations after adjustments for covariates suggests that the obesogenic effects of TV viewing are partly mediated by other lifestyle factors.
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Affiliation(s)
- I Heinonen
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
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Pal S, Radavelli-Bagatini S. The effects of whey protein on cardiometabolic risk factors. Obes Rev 2013; 14:324-43. [PMID: 23167434 DOI: 10.1111/obr.12005] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 10/16/2012] [Accepted: 10/16/2012] [Indexed: 12/12/2022]
Abstract
Obesity has reached epidemic proportions worldwide. The health consequences of obesity are more dangerous when associated with the metabolic syndrome and its components. Studies show that whey protein and its bioactive components can promote greater benefits compared to other protein sources such as egg and casein. The aim of this paper is to review the effects of whey protein on cardiometabolic risk factors. Using PubMed as the database, a review was conducted to identify current scientific literature on whey protein and the components of the metabolic syndrome published between 1970 and 2012. Consumption of whey protein seems to play an anti-obesity and muscle-protective role during dieting by increasing thermogenesis and maintaining lean mass. In addition, whey protein has been shown to improve glucose levels and insulin response, promote a reduction in blood pressure and arterial stiffness, and improve lipid profile. The collective view of current scientific literature indicates that the consumption of whey protein may have beneficial effects on some symptoms of the metabolic syndrome as well as a reduction in cardiovascular risk factors.
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Affiliation(s)
- Sebely Pal
- School of Public Health, Curtin Health Innovation Research Institute, Curtin University of Technology, Perth, Western Australia, Australia.
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30
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Sato JN, Wagle A, McProud L, Lee L. Food Label Effects on Customer Purchases in a Hospital Cafeteria in Northern California. ACTA ACUST UNITED AC 2013. [DOI: 10.1080/15378020.2013.782235] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Kramarow E, Lubitz J, Francis R. Trends in the coronary heart disease risk profile of middle-aged adults. Ann Epidemiol 2013; 23:31-4. [PMID: 23176783 PMCID: PMC11309520 DOI: 10.1016/j.annepidem.2012.10.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 09/14/2012] [Accepted: 10/24/2012] [Indexed: 11/19/2022]
Abstract
PURPOSE To examine recent trends in the coronary heart disease (CHD) risk profiles of the population aged 45 to 64 in the United States. METHODS Data from the National Health and Nutrition Examination Surveys (NHANES) from 2 time periods (1988-1994 and 2005-2008) are used to estimate the CHD risk functions derived from the Framingham Heart Study. The risk functions take account of levels of blood pressure (systolic and diastolic), total and high-density lipoprotein serum cholesterol, diabetes (doctor diagnosed or based on fasting glucose), and smoking status to estimate the 10-year risk of myocardial infarction or coronary death. We estimate the risk functions by gender, race, and age group (45-54 and 55-64). RESULTS The CHD risk profile of middle-aged adults has improved over time. For example, the mean 10-year risk of heart attack or CHD death among persons 55 to 64 years has declined from 7.1% to 5.2%. Declines are seen among both men and women and among non-Hispanic Blacks and non-Hispanic whites. CONCLUSIONS Despite increases in diabetes and obesity, the CHD risk profile of middle-aged adults improved during the period from 1988-1994 to 2005-2008.
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Affiliation(s)
- Ellen Kramarow
- Aging and Chronic Disease Statistics Branch, Office of Analysis and Epidemiology, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD, USA.
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Karlsson EA, Marcelin G, Webby RJ, Schultz‐Cherry S. Review on the impact of pregnancy and obesity on influenza virus infection. Influenza Other Respir Viruses 2012; 6:449-60. [PMID: 22335790 PMCID: PMC4941607 DOI: 10.1111/j.1750-2659.2012.00342.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness.
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Affiliation(s)
| | | | - Richard J. Webby
- Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, TN, USA
| | - Stacey Schultz‐Cherry
- Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, TN, USA
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Abstract
A growing number of studies have shown that a diet high in long chain SFA and/or obesity cause profound changes to the energy balance centres of the hypothalamus which results in the loss of central leptin and insulin sensitivity. Insensitivity to these important anorexigenic messengers of nutritional status perpetuates the development of both obesity and peripheral insulin insensitivity. A high-fat diet induces changes in the hypothalamus that include an increase in markers of oxidative stress, inflammation, endoplasmic reticulum (ER) stress, autophagy defect and changes in the rate of apoptosis and neuronal regeneration. In addition, a number of mechanisms have recently come to light that are important in the hypothalamic control of energy balance, which could play a role in perpetuating the effect of a high-fat diet on hypothalamic dysfunction. These include: reactive oxygen species as an important second messenger, lipid metabolism, autophagy and neuronal and synaptic plasticity. The importance of nutritional activation of the Toll-like receptor 4 and the inhibitor of NF-κB kinase subunit β/NK-κB and c-Jun amino-terminal kinase 1 inflammatory pathways in linking a high-fat diet to obesity and insulin insensitivity via the hypothalamus is now widely recognised. All of the hypothalamic changes induced by a high-fat diet appear to be causally linked and inhibitors of inflammation, ER stress and autophagy defect can prevent or reverse the development of obesity pointing to potential drug targets in the prevention of obesity and metabolic dysfunction.
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Lawrence NS, Hinton EC, Parkinson JA, Lawrence AD. Nucleus accumbens response to food cues predicts subsequent snack consumption in women and increased body mass index in those with reduced self-control. Neuroimage 2012; 63:415-22. [PMID: 22776461 DOI: 10.1016/j.neuroimage.2012.06.070] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 06/28/2012] [Accepted: 06/30/2012] [Indexed: 01/01/2023] Open
Abstract
Individuals have difficulty controlling their food consumption, which is due in part to the ubiquity of tempting food cues in the environment. Individual differences in the propensity to attribute incentive (motivational) salience to and act on these cues may explain why some individuals eat more than others. Using fMRI in healthy women, we found that food cue related activity in the nucleus accumbens, a key brain region for food motivation and reward, was related to subsequent snack food consumption. However, both nucleus accumbens activation and snack food consumption were unrelated to self-reported hunger, or explicit wanting and liking for the snack. In contrast, food cue reactivity in the ventromedial prefrontal cortex was associated with subjective hunger/appetite, but not with consumption. Whilst the food cue reactivity in the nucleus accumbens that predicted snack consumption was not directly related to body mass index (BMI), it was associated with increased BMI in individuals reporting low self-control. Our findings reveal a neural substrate underpinning automatic environmental influences on consumption in humans and demonstrate how self-control interacts with this response to predict BMI. Our data provide support for theoretical models that advocate a 'dual hit' of increased incentive salience attribution to food cues and poor self-control in determining vulnerability to overeating and overweight.
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Affiliation(s)
- Natalia S Lawrence
- School of Psychology, Cardiff University, Park Place, Cardiff CF10 3AT, UK.
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35
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Choquette AC, Bouchard L, Drapeau V, Lemieux S, Tremblay A, Bouchard C, Vohl MC, Pérusse L. Association between olfactory receptor genes, eating behavior traits and adiposity: Results from the Quebec Family Study. Physiol Behav 2012; 105:772-6. [DOI: 10.1016/j.physbeh.2011.10.015] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2011] [Revised: 10/13/2011] [Accepted: 10/14/2011] [Indexed: 12/01/2022]
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Velkoska E, Morris MJ. Mechanisms behind early life nutrition and adult disease outcome. World J Diabetes 2011; 2:127-32. [PMID: 21954416 PMCID: PMC3180529 DOI: 10.4239/wjd.v2.i8.127] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Revised: 08/11/2011] [Accepted: 08/14/2011] [Indexed: 02/05/2023] Open
Abstract
Obesity is increasing around the globe. While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following under- and over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures such as undernutrition and altered metabolic and hormonal signals, in utero exposure to altered maternal nutrition and inadequate nutrition during early postnatal life may contribute to programming of obesity in offspring. Data from animal studies indicate both intrauterine and postnatal environments are critical determinants of the development of pathways regulating energy homeostasis. This review summarizes recent evidence of the impact of maternal nutrition as well as postnatal nutrition of the offspring on subsequent obesity and disease risk of the offspring. While much of the experimental work reviewed here was conducted in the rodent, these observations provide useful insights into avenues for future research into developing preventive measures to curb the obesity epidemic.
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Affiliation(s)
- Elena Velkoska
- Elena Velkoska, Department of Medicine, The University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg Heights, 3081, Victoria, Australia
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37
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Abstract
The world is now experiencing an epidemic of obesity. Although the effects of obesity on the development of metabolic and cardiovascular problems are well studied, much less is known about the impact of obesity on immune function and infectious disease. Studies in obese humans and with obese animal models have repeatedly demonstrated impaired immune function, including decreased cytokine production, decreased response to antigen/mitogen stimulation, reduced macrophage and dendritic cell function, and natural killer cell impairment. Recent studies have demonstrated that the impaired immune response in the obese host leads to increased susceptibility to infection with a number of different pathogens such as community-acquired tuberculosis, influenza, Mycobacterium tuberculosis, coxsackievirus, Helicobacter pylori and encephalomyocarditis virus. While no specific mechanism has been defined for the decreased immune response to infectious disease in the obese host, several obesity-associated changes such as excessive inflammation, altered adipokine signaling, metabolic changes and even epigenetic regulation could affect the immune response. This review will discuss what is currently known about the relationship between obesity and infectious disease.
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Affiliation(s)
- Erik A Karlsson
- Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105-3678
| | - Melinda A Beck
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7461, USA
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Karlsson EA, Sheridan PA, Beck MA. Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells. J Nutr 2010; 140:1691-7. [PMID: 20592105 PMCID: PMC2924599 DOI: 10.3945/jn.110.123653] [Citation(s) in RCA: 94] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8(+) memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor beta (IL-2R beta, CD122), but not IL-7 receptor alpha (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population.
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Li D, Sun WP, Zhou YM, Liu QG, Zhou SS, Luo N, Bian FN, Zhao ZG, Guo M. Chronic niacin overload may be involved in the increased prevalence of obesity in US children. World J Gastroenterol 2010; 16:2378-87. [PMID: 20480523 PMCID: PMC2874142 DOI: 10.3748/wjg.v16.i19.2378] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2009] [Revised: 03/14/2010] [Accepted: 03/21/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate nicotinamide's action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS Dynamic nicotinamide's effect on plasma hydrogen peroxide and glucose metabolism was investigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects. Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively. RESULTS Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 +/- 0.1 micromol/L vs 1.6 +/- 0.1 micromol/L, P = 0.016) and insulin levels (247.1 +/- 129.0 pmol/L vs 452.6 +/- 181.8 pmol/L, P = 0.028) were significantly higher, and the 3-h blood glucose was significantly lower (5.8 +/- 1.2 mmol/L vs 4.5 +/- 1.1 mmol/L, P = 0.002) after co-administration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R(2) = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively). CONCLUSION The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.
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Larter CZ, Chitturi S, Heydet D, Farrell GC. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol 2010; 25:672-90. [PMID: 20492324 DOI: 10.1111/j.1440-1746.2010.06253.x] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The strong relationship between over-nutrition, central obesity, insulin resistance/metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) suggest pathogenic interactions, but key questions remain. NAFLD starts with over-nutrition, imbalance between energy input and output for which the roles of genetic predisposition and environmental factors (diet, physical activity) are being redefined. Regulation of energy balance operates at both central nervous system and peripheral sites, including adipose and liver. For example, the endocannabinoid system could potentially be modulated to provide effective pharmacotherapy of NAFLD. The more profound the metabolic abnormalities complicating over-nutrition (glucose intolerance, hypoadiponectinemia, metabolic syndrome), the more likely is NAFLD to take on its progressive guise of non-alcoholic steatohepatitis (NASH). Interactions between steatosis and insulin resistance, visceral adipose expansion and subcutaneous adipose failure (with insulin resistance, inflammation and hypoadiponectinemia) trigger amplifying mechanisms for liver disease. Thus, transition from simple steatosis to NASH could be explained by unmitigated hepatic lipid partitioning with failure of local adaptive mechanisms leading to lipotoxicity. In part one of this review, we discuss newer concepts of appetite and metabolic regulation, bodily lipid distribution, hepatic lipid turnover, insulin resistance and adipose failure affecting adiponectin secretion. We review evidence that NASH only occurs when over-nutrition is complicated by insulin resistance and a highly disordered metabolic milieu, the same 'metabolic movers' that promote type 2 diabetes and atheromatous cardiovascular disease. The net effect is accumulation of lipid molecules in the liver. Which lipids and how they cause injury, inflammation and fibrosis will be discussed in part two.
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Abstract
OBJECTIVE Using Wakefield's conceptualization of mental disorder as "harmful mental dysfunction" (Wakefield, Am Psychol, 47, 373-388, 1992), we examined the evidence for including obesity as a mental disorder in DSM-V. METHOD We searched computer databases and examined reference lists from review articles published in the last 10 years to identify empirical papers relevant to the present review. RESULTS Obesity is a condition of heterogeneous etiology that is harmful for most individuals. However, there is scant evidence that obesity, in general, is caused by mental dysfunction. Although recent work examining the neurocircuitry of energy balance has suggested that mental dysfunction may be involved in the etiology of specific obesity phenotypes, findings are too preliminary to support classification of obesity as a mental disorder. Nevertheless, there is evidence that obesity is related to mental disorder and many of the medications used to treat psychiatric illness. DISCUSSION There is little evidence for including obesity as a mental disorder in DSM-V. However, results confirm the importance of monitoring adiposity routinely among patients with psychiatric illness.
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Affiliation(s)
- Marsha D Marcus
- Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
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43
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Morris MJ. Early life influences on obesity risk: maternal overnutrition and programming of obesity. Expert Rev Endocrinol Metab 2009; 4:625-637. [PMID: 30780787 DOI: 10.1586/eem.09.45] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures, such as undernutrition and altered metabolic and hormonal signals, in utero exposure to maternal obesity-related changes may contribute to programming of obesity in offspring. Data from animal studies indicate both intrauterine and postnatal environments are critical determinants of the development of pathways regulating energy homeostasis. This review summarizes recent evidence of the impact of maternal obesity on subsequent obesity risk, paying particular attention to the hypothalamic regulation of appetite and markers of metabolic control. The extraordinary rise in the rates of maternal obesity underlines an urgent need to investigate the mechanisms contributing to its transgenerational effects.
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Affiliation(s)
- Margaret J Morris
- a Department of Pharmacology, School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
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Abstract
It is well established that the development of NAFLD and NASH are closely linked to an excess flow of free fatty acids (FFA) arising from dysfunctional/insulin resistant adipose tissue causing ectopic fat deposition in many organs. In the liver, when chronic lipid supply surpasses the metabolic ability to adapt it will induce hepatocellular damage as FFA are redirected into harmful pathways of non-oxidative metabolism with intracellular accumulation of toxic lipid-derived metabolites. Multiple mechanisms have been implicated including mitochondrial dysfunction, endoplasmic reticulum stress, and activation of multiple inflammatory pathways. Understanding the role of insulin resistance and lipotoxicity in NASH as part of a broader metabolic disorder is likely to assist practitioners in the successful management of these challenging patients.
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Affiliation(s)
- Kenneth Cusi
- Diabetes Division, The University of Texas Health Science Center at San Antonio, Room 3.380S, 7703 Floyd Curl Drive, San Antonio, TX 78284-3900, USA.
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Choquette AC, Lemieux S, Tremblay A, Drapeau V, Bouchard C, Vohl MC, Pérusse L. GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study. Physiol Behav 2009; 98:505-10. [DOI: 10.1016/j.physbeh.2009.08.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2009] [Revised: 04/23/2009] [Accepted: 08/06/2009] [Indexed: 10/20/2022]
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Shiraev T, Chen H, Morris MJ. Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators. J Neuroendocrinol 2009; 21:602-9. [PMID: 19490368 DOI: 10.1111/j.1365-2826.2009.01877.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague-Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.
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Affiliation(s)
- T Shiraev
- Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
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Abstract
OBJECTIVE The present study describes the trajectory of the energy gap (energy imbalance) in the Canadian population from 1976 to 2003, its temporal relationship to adult obesity, and estimates the relative contribution of energy availability and expenditure to the energy gap. It also assesses which foods contributed the most to changes in available energy over the study period. DESIGN Annual estimates of the energy gap were derived by subtracting population-adjusted per capita daily estimated energy requirements (derived from Dietary Reference Intakes) from per capita daily estimated energy available (obtained from food balance sheets). Food balance sheets were used to assess which foods contributed to changes in energy availability. Adult obesity rates were derived from six national surveys. The relationship to the energy gap was assessed through regression analysis. RESULTS Between 1976 and 2003, per capita daily estimated energy availability increased by 18 % (1744 kJ), and increased energy availability was the major driver of the increased energy gap. Salad oils, wheat flour, soft drinks and shortening accounted for the majority of the net increase in energy availability. Adult obesity was significantly correlated with the energy gap over the study period. CONCLUSIONS The widening energy gap is being driven primarily by increased energy availability. The food commodities driving the widening energy gap are major ingredients in many energy-dense convenience foods, which are being consumed with increasing frequency in Canada. Policies to address population obesity must have a strong nutritional focus with the objective of decreasing energy consumption at the population level.
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Teske JA, Kotz CM. Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats. Am J Physiol Regul Integr Comp Physiol 2009; 297:R176-84. [PMID: 19420294 DOI: 10.1152/ajpregu.90866.2008] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Caloric restriction (CR) and metabolic glucoprivation affect spontaneous physical activity (SPA), but it's unknown whether these treatments similarly affect SPA in selectively bred obesity-prone (OP) and -resistant (OR) rats. OR rats have greater basal SPA and are more responsive to treatments that modulate SPA, such as orexin A administration. We hypothesized that OR rats would be more sensitive to other treatments modulating SPA. To test this, continuous 24-h SPA was measured before and during acute (24 h) and chronic (8 wk) CR in OR, OP, and Sprague-Dawley rats. Pharmacological glucoprivation was produced by injection of 2-deoxyglucose (2-DG), and SPA was measured 5 h postinjection. Acute CR increased SPA in all groups; however, the effect was dependent on the index of SPA and time interval during the 24-h time period. In contrast to OR rats, chronic CR increased distance traveled, ambulatory episodes, and time spent in ambulation and stereotypy during the time interval preceding anticipation of food in OP and Sprague-Dawley rats. Although the effects of 2-DG treatment on SPA were minimal, OR rats had significantly greater SPA than OP and Sprague-Dawley rats independent of treatment. That chronic CR failed to result in significant changes in SPA in OR rats suggests that these rats may be especially unresponsive to treatments modulating feeding. This insensitivity coupled with elevated basal SPA levels may in part mediate phenotypic traits of lean rats.
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Affiliation(s)
- J A Teske
- University of Minnesota, Department of Food Science and Nutrition, St. Paul, Minnesota, USA.
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O'Sullivan AJ. Does oestrogen allow women to store fat more efficiently? A biological advantage for fertility and gestation. Obes Rev 2009; 10:168-77. [PMID: 19021869 DOI: 10.1111/j.1467-789x.2008.00539.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In normal healthy-weight humans, women have a higher percentage body fat than men, a difference that commences at puberty and continues throughout adult life, suggesting that the mechanism is related to sex steroids. The first half of pregnancy is also a stage of body fat gain in women. From an energy balance point, there is no explanation why women should be fatter than men, as the latter consume more calories proportionately. Moreover, women store fat in early pregnancy when caloric intake does not significantly change. The aim of this review is to focus on evidence supporting one mechanism that may account for these findings. That is, oestrogen reduces postprandial fatty acid oxidation leading to an increase in body fat which may account for the greater fat mass observed in women compared with men and the fat gain in early pregnancy. Therefore, female puberty and early pregnancy could be seen as states of efficient fat storage of energy in preparation for fertility, foetal development and lactation providing an obvious biological advantage. Further research into this mechanism of fat storage may provide further insights into the regulation of body fat.
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Affiliation(s)
- A J O'Sullivan
- Department of Medicine, St George Hospital, University of New South Wales, Sydney, Australia.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of referral to liver clinics, and its progressive form, non-alcoholic steatohepatitis (NASH), can lead to cirrhosis and end-stage liver disease. The main risk factors for NAFLD/NASH are the metabolic abnormalities commonly observed in metabolic syndrome: insulin resistance, visceral obesity, dyslipidemia and altered adipokine profile. At present, the causes of progression from NAFLD to NASH remain poorly defined, and research in this area has been limited by the availability of suitable animal models of this disease. In the past, the main models used to investigate the pathogenesis of steatohepatitis have either failed to reproduce the full spectrum of liver pathology that characterizes human NASH, or the liver pathology has developed in a metabolic context that is not representative of the human condition. In the last few years, a number of models have been described in which the full spectrum of liver pathology develops in an appropriate metabolic context. In general, the underlying cause of metabolic defects in these models is chronic caloric overconsumption, also known as overnutrition. Overnutrition has been achieved in a number of different ways, including forced feeding, administration of high-fat diets, the use of genetically hyperphagic animals, or a combination of these approaches. The purpose of the present review is to critique the liver pathology and metabolic abnormalities present in currently available animal models of NASH, with particular focus on models described in approximately the last 5 years.
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Affiliation(s)
- Claire Z Larter
- ANU Medical School, Australian National University at The Canberra Hospital, Canberra, ACT, Australia.
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