Long-term High-fat Diet Consumption Research Articles

Effects of chronic exposure to a high fat diet, nutritive or non-nutritive sweeteners on hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes of male Sprague-Dawley rats.

Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.

Impact of Aging and High-Fat Diet on Adipose Tissue-Derived Extracellular Vesicle miRNA Profiles in Mice

Background: Middle-aged adults show the highest obesity rates, leading to significant health complications in later years. Obesity triggers the release of altered molecules including extracellular vesicles (EVs) from excess adipose tissue (AT), contributing to various health complications. In this study, we assessed the effects of age and high-fat diet (HFD) on white AT-derived EV miRNA profiles to understand their potential roles in aging and obesity. Hypothesis: Our hypothesis is that the white AT-derived EV miRNA profiles of middle-aged mice fed HFD will demonstrate deleterious features due to the potential synergistic effects of aging and long-term HFD consumption. Method: C57BL/6 male mice were subjected to a normal chow diet (NCD) or a HFD for either 10-12 weeks (young mice, n=10) or 50-61 weeks (middle-aged mice, n=12). After evaluating metabolic characteristics, white AT-derived EV miRNAs were profiled using a NanoString miRNA panel (n=599). Results: Middle-aged mice exhibited obesity regardless of diet. Young mice fed HFD showed similar metabolic traits to middle-aged mice. In NCD group, 131 differentially expressed miRNAs (DE-miRNAs) emerged in middle-aged mice compared to young mice, including miR-21, miR-148a, and miR-29a associated with cancer, neuro/psychological disorders and reproductive diseases. In HFD group, 55 DE-miRNAs were revealed in middle-aged mice compared to young mice. These miRNAs were associated with significantly suppressed IGF1R activity. Conclusion: This study has demonstrated the altered characteristics of WAT EV miRNAs by aging and diet. Aging and diet induce significant changes in EV miRNA profiles of AT. We suggest that there might be a selective sorting mechanism of miRNAs in AT EVs, contributing to the disease progress or pathogenesis related to aging and obesity. We also suggest that AT EVs in middle-aged mice fed HFD might play a protective role in aging and obesity by inhibiting IGF1R activity. University of Iowa College of Nursing. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

High-fat diet feeding triggers a regenerative response in the adult zebrafish brain.

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/β-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.

Prolonged High-Fat Diet Consumption throughout Adulthood in Mice Induced Neurobehavioral Deterioration via Gut-Brain Axis.

Neuropsychiatric disorders have been one of the worldwide health problems contributing to profound social and economic consequences. It is reported that consumption of an excessive high-fat diet (HFD) in middle age could induce cognitive and emotional dysfunctions, whereas the mechanisms of the effects of long-term HFD intake on brain disorders have not been fully investigated. We propose a hypothesis that prolonged HFD intake throughout adulthood could lead to neurobehavioral deterioration via gut-brain axis. In this study, the adult C57BL/6J mice consuming long-term HFD (24 weeks) exhibited more anxiety-like, depression-like, and disruptive social behaviors and poorer performance in learning and memory than control mice fed with a normal diet (ND). In addition, the homeostasis of gut microbiota was impaired by long-term HFD consumption. Changes in some flora, such as Prevotellaceae_NK3B31_group and Ruminococcus, within the gut communities, were correlated to neurobehavioral alterations. Furthermore, the gut permeability was increased after prolonged HFD intake due to the decreased thickness of the mucus layer and reduced expression of tight junction proteins in the colon. The mRNA levels of genes related to synaptic-plasticity, neuronal development, microglia maturation, and activation in the hippocampus and prefrontal cortex of HFD-fed mice were lower than those in mice fed with ND. Interestingly, the transcripts of genes related to tight junction proteins, ZO-1 and Occludin involved in blood-brain-barrier (BBB), were decreased in both hippocampus and prefrontal cortex after long-term HFD consumption. Those results indicated that chronic consumption of HFD in mice resulted in gut microbiota dysbiosis, which induced decreased expression of mucus and tight junction proteins in the colon, in turn leading to local and systemic inflammation. Those changes could further contribute to the impairment of brain functions and neurobehavioral alterations, including mood, sociability, learning and memory. In short, long-term HFD intake throughout adulthood could induce behavioral phenotypes related to neuropsychiatric disorders via gut-brain axis. The observations of this study provide potential intervention strategies to reduce the risk of HFD via targeting the gut or manipulating gut microbiota.

Long-Term High-Fat Diet Consumption Induces Cognitive Decline Accompanied by Tau Hyper-Phosphorylation and Microglial Activation in Aging

High-fat diet (HFD) intake is commonly related to a substantial risk of cognitive impairment for senior citizens over 65 years of age, which constitutes a profound global health burden with several economic and social consequences. It is critical to investigate the effects of long-term HFD consumption on cognitive function and to inspect the potential underlying mechanisms. In the present study, 9-month-old male C57BL/6 mice were randomly assigned to either a normal diet (ND, 10 kcal% fat) or an HFD diet (60 kcal% fat) for 10 months. Then a series of behavioral tests, and histological and biochemistry examinations of the hippocampus and cortex proceeded. We found that long-term HFD-fed aged mice exhibited cognitive function decline in the object place recognition test (OPR). Compared with the ND group, the HFD-fed mice showed Tau hyperphosphorylation at ps214 in the hippocampus and at ps422 and ps396 in the cortex, which was accompanied by GSK-3β activation. The higher activated phenotype of microglia in the brain of the HFD group was typically evidenced by an increased average area of the cell body and reduced complexity of microglial processes. Immunoblotting showed that long-term HFD intake augmented the levels of inflammatory cytokines IL-6 in the hippocampus. These findings indicate that long-term HFD intake deteriorates cognitive dysfunctions, accompanied by Tau hyperphosphorylation, microglial activation, and inflammatory cytokine expression, and that the modifiable lifestyle factor contributes to the cognitive decline of senior citizens.

High Fat Diet Mediates Amyloid-β Cleaving Enzyme 1 Phosphorylation and SUMOylation, Enhancing Cognitive Impairment in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common form of dementia in older adults and extracellular accumulation of amyloid-β (Aβ) is one of the two characterized pathologies of AD. Obesity is significantly associated with AD developing factors. Several studies have reported that high fat diet (HFD) influenced Aβ accumulation and cognitive performance during AD pathology. However, the underlying neurobiological mechanisms have not yet been elucidated. The objective of this study was to explore the underlying neurobiological mechanisms of HFD influenced Aβ accumulation and cognitive performance during AD pathology. 2.5-month-old male APP/PS1 mice were randomly separated into two groups: 1) the normal diet (ND) group, fed a standard diet (10 kcal%fat); and 2) the HFD group, fed a high fat diet (40 kcal%fat, D12492; Research Diets). After 4 months of HFD or ND feeding, mice in the two groups were subjected for further ethological, morphological, and biochemical analyses. A long-term HFD diet significantly increased perirenal fat and impaired dendritic integrity and aggravated neurodegeneration, and augmented learning and memory deficits in APP/PS1 mice. Furthermore, the HFD increased beta amyloid cleaving enzyme 1 (BACE1) dephosphorylation and SUMOylation, resulting in enhanced enzyme activity and stability, which exacerbated the deposition of amyloid plaques. Our study demonstrates that long-term HFD consumption aggravates amyloid-β accumulation and cognitive impairments, and that modifiable lifestyle factors, such as obesity, can induce BACE1 post-modifications which may contribute to AD pathogenesis.

Long-Term High-Fat Diet Consumption Depletes Glial Cells and Tyrosine Hydroxylase-Containing Neurons in the Brain of Middle-Aged Rats.

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of neuronal degeneration. However, the effects of chronic dyslipidemia on brain function, especially in older individuals, remain unclear. In this study, middle-aged 37-week-old male Wistar-Kyoto rats were fed a normal diet (ND) or a 45% high-fat diet (HFD) for 30 weeks (i.e., until 67 weeks of age). To study the effects of chronic dyslipidemia on the brain, we analyzed spontaneous locomotor activity, cognitive function, and brain tissues in both groups of rats after 30 weeks. Compared with age-matched rats fed a ND, Wistar-Kyoto rats fed a HFD had dyslipidemia and showed decreased movement but normal recognition of a novel object. In our brain analyses, we observed a significant decrease in astrocytes and tyrosine hydroxylase–containing neurons in the substantia nigra and locus coeruleus of rats fed a HFD compared with rats fed a ND. However, hippocampal pyramidal neurons were not affected. Our findings indicate that the long-term consumption of a HFD may cause lipid metabolism overload in the brain and damage to glial cells. The decrease in astrocytes may lead to reduced protection of the brain and affect the survival of tyrosine hydroxylase–containing neurons but not pyramidal neurons of the hippocampus.

High‐fat diet reduced dendritic spine density, but it did not affect cognitive function in spontaneous diabetic torii rats

Diabetes is a known risk factor for dementia, several factors are involved in the pathogenesis of diabetes including genetic predisposition, and high calorie diet consumption. We previously reported that long-term high-fat diet (HFD) consumption led to prediabetes, which associated with cognitive impairments. However, the effects of long-term HFD consumption on metabolic and brain function in genetically type 2 diabetes (T2DM) model have not been investigated. Therefore, we hypothesized that long-term HFD consumption aggravates metabolic and cognitive impairments in T2DM rats. Sixteen Spontaneous Diabetic Torii (SDT) rats, which is a genetically engineered T2DM rats, and eight wild type (WT) rats were used. At the age of 8 weeks old, SDT rats were divided into two dietary groups either normal diet or HFD feeding for 12 weeks. WT rats were received a normal diet entire the study. At 20 weeks old, metabolic parameters, the hippocampal dependent cognitive function using novel object location (NOL) test, and hippocampal dendritic spine density were determined. Our data demonstrated that, at 20 weeks old, SDT rats in both dietary groups exhibited their diabetic characters as indicated by hyperglycemia, hypoinsulinemia, and insulin insensitivity. HFD feeding did not aggravate diabetic status, but it significantly induced body weight gain, visceral fat deposition, hypertriglyceridemia, and hypercholesterolemia (as shown in Figure 1). Unexpectedly, hippocampal dependent cognitive impairments were not observed in both normal diet and HFD-fed SDT rats, when compared with WT rats (Figure 1). However, brain mitochondrial dysfunction and dendritic spine loss were observed in both dietary groups of SDT rats. Interestingly, the reduction of dendritic spine density was greater in HFD-fed SDT rats than normal diet-fed SDT rats (Figure 1). Long-term HFD consumption induced truncal obesity, dyslipidemia, and reduced dendritic spine density in SDT rats, but it did not affect hippocampal dependent cognitive function. It is possible that the duration of HFD feeding was insufficient to promote cognitive impairments in genetically T2DM rats.

Long-term high-fat diet consumption by mice throughout adulthood induces neurobehavioral alterations and hippocampal neuronal remodeling accompanied by augmented microglial lipid accumulation

High-fat diet (HFD) consumption is generally associated with an increased risk of cognitive and emotional dysfunctions that constitute a sizeable worldwide health burden with profound social and economic consequences. Middle age is a critical time period that affects one’s health later in life; pertinently, the prevalence of HFD consumption is increasing among mature adults. Given the growing health-related economic burden imposed globally by increasing rates of noncommunicable diseases in rapidly aging populations, along with the pervasive but insidious health impairments associated with HFD consumption, it is critically important to understand the effects of long-term HFD consumption on brain function and to gain insights into their potential underlying mechanisms. In the present study, adult male C57BL/6J mice were randomly assigned a control diet (CD, 10 kJ% from fat) or an HFD (60 kJ% from fat) for 6 months (6 M) or 9 months (9 M) followed by behavioral tests, serum biochemical analysis, and histological examinations of both the dorsal and ventral regions of the hippocampus. In both the 6 M and 9 M cohorts, mice that consumed an HFD exhibited poorer memory performance in the Morris water maze test (MWM) and greater depression- and anxiety-like behavior during the open field test (OFT), sucrose preference test (SPT) and forced swim test (FST) than control mice. Compared with age-matched mice in the CD group, mice in the HFD group showed abnormal hippocampal neuronal morphology, which was particularly evident in the ventral hippocampus. Hippocampal microglia in mice in the HFD group generally had a more activated phenotype evidenced by a smaller microglial territory area and increased cluster of differentiation 68 (CD68, a marker of phagocytic activity) immunoreactivity, while the microglial density in the dentate gyrus (DG) was decreased, indicating microglial decline. The engulfment of postsynaptic density 95 (PSD95, a general postsynaptic marker) puncta by microglia was increased in the HFD groups. Histological analysis of neutral lipids using a fluorescent probe (BODIPY) revealed that the total neutral lipid content in regions of interests (ROIs) and the lipid load in microglia were increased in the HFD group relative to the age-matched CD group. In summary, our results demonstrated that chronic HFD consumption from young adulthood to middle age induced anxiety- and depression-like behavior as well as memory impairment. The negative influence of chronic HFD consumption on behavioral and hippocampal neuroplasticity appears to be linked to a change in microglial phenotype that is accompanied by a remarkable increase in cellular lipid accumulation. These observations highlighting the potential to target lipid metabolism deficits to reduce the risk of HFD-associated emotional dysfunctions.

Long-term high fat diet consumption reversibly alters feeding behavior via a dopamine-associated mechanism in mice

Obesity is a costly, global epidemic that is perpetuated by an unhealthy diet. A significant factor in the initial consumption and maintenance of an unhealthy diet is the abundance of highly palatable, calorically dense foods. The aim of the present study is to better understand the effects of high fat diet (HFD) consumption on food valuation and preference, and to elucidate the neurobiological mechanisms mediating these effects. By using a novel food preference assay, we found that prolonged consumption of a HFD diminishes preference for and consumption of the more calorically dense food choice when two lab diets are presented. Additionally, we demonstrated that prolonged HFD consumption dampens ventral tegmental c-fos induction during hedonic feeding, implicating the mesolimbic dopamine signaling pathway as a target of HFD. Notably, both the changes in food preference and this reduced c-fos induction were reversed during withdrawal from HFD. Further, HFD-induced alterations in food preference were attenuated by exercise. Our findings suggest that prolonged HFD consumption leads to anhedonia and altered feeding choices, and this is associated with changes in mesolimbic dopamine signaling.

Effect and mechanism of high-fat diet on the preference for sweeteners on mice.

Male Kunming mice were divided into a normal diet group (control group) and a high-fat diet group (HF group) (185 g·kg-1 protein, 600 g·kg-1 fat and 205 g·kg-1 carbohydrate). After 8 weeks' feeding, behavioral indicators and biochemical indicators in serum were determined. The double-bottle preference experiment was used to study the preferences of mice for five sweeteners. The monoamine neurotransmitter content, gene expression related to dopamine (DA), and opioid receptors were also determined. The body weight of the mice in the HF group increased significantly (P < 0.05) after 36 days compared with the control group. The feed intake of the HF group increased sharply in the first 12 days, and then it became basically unchanged. The preference of the HF group for all of the five sweeteners was highly significantly lower (P < 0.01) than that of the control group. Depression-related behavior was observed in the HF group mice. The triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDLC) content in the HF group were very much higher (P < 0.01) than those of the control group. The gene expression related to DA and opioid receptor in the HF group was significantly lower than that of the control group, except for preproenkephalin (PENK). In summary, this study suggested that a long-term high-fat diet could result in a decrease in the preference for sweeteners and could result in a state of reward hypofunction in mice. © 2020 Society of Chemical Industry.

Ad libitum high fat diet consumption during adolescence and adulthood fails to impact the affective properties of cocaine in male Sprague-Dawley rats.

Recent research from our laboratories has demonstrated that long-term and ad libitum high fat diet (HFD) consumption during adolescence and adulthood increases the intravenous self-administration (IVSA) of cocaine in adult male Sprague-Dawley rats. One possible interpretation of these findings is that this dietary history influences the affective properties of cocaine, that is, cocaine's rewarding and/or aversive effects. In this context, our research and others suggest that the overall affective response to a drug, and its potential for use and abuse, reflects a balance between these properties in which the rewarding effects of a drug maintain its use and the aversive effects limit it. Accordingly, long-term HFD consumption might increase the rewarding effects of cocaine and/or decrease its aversive effects, resulting in greater IVSA. To examine this possibility, male Sprague-Dawley rats were maintained on either a HFD (n = 32) or chow diet (n = 32) beginning on postnatal day (PND) 21 and underwent combined cocaine-induced place preference and taste avoidance conditioning from PNDs 78-102. Under these conditions, cocaine (18 and 32 mg/kg, intraperitoneally [IP]), but not vehicle, was effective in inducing both a place preference and a taste avoidance; however, HFD- and chow-fed animals did not differ on either of these behavioral indices. These data suggest that the ability of ad libitum HFD consumption during adolescence to increase cocaine IVSA is not likely due to changes in the affective properties of cocaine. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

PCSK9 inhibitor effectively attenuates cardiometabolic impairment in obese-insulin resistant rats

Long-term high-fat diet consumption causes obese-insulin resistance and cardiac mitochondrial dysfunction, leading to impaired left ventricular (LV) function. Atorvastatin effectively improved lipid profiles in obese patients. However, inadequate reduction in low density lipoprotein cholesterol (LDL-C) level was found. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor effectively reduced LDL-C levels. We hypothesized that this PCSK9 inhibitor has a greater efficacy in attenuating cardiometabolic impairments than atorvastatin in obese-insulin resistant rats. Female rats were fed with either a high fat or normal diet for 12 weeks. High fat diet fed rats (HFD) were then divided into 3 groups and were given vehicle, atorvastatin (40 mg/kg/day; s.c.), or PCSK9 inhibitor (4 mg/kg/day; s.c.) for additional 3 weeks. The metabolic parameters, cardiac and mitochondrial function and [Ca2+]i transients were determined. HFD rats developed obese-insulin resistance as indicated by increased plasma insulin and HOMA index. Although high-fat diet fed rats treated with vehicle (HFV) rats had markedly impaired LV function as indicated by reduced %LVFS, impaired cardiac mitochondrial function, and [Ca2+]i transient regulation, these impairments were attenuated in high-fat diet fed rats treated with atorvastatin (HFA) and high-fat diet fed rats treated with PCSK9 inhibitor (HFP) rats. However, these improvements were greater in HFP rats than HFA rats. Our findings indicated that the PCSK9 inhibitor exerted greater cardioprotection than atorvastatin through improved mitochondrial function in obese-insulin resistant rats.

Alterations of aorta intima and media transcriptome in swine fed high-fat diet over 1-year follow-up period and of the switch to normal diet

Background and aimWe previously showed that 12-month high-fat diet (HFD) in pigs led to fattening and increased artery intima-media-thickness, which were partly reversed after 3-month return to control diet (CD). The aim of this study was to decipher underlying mechanism of action by using transcriptomic analyses of intima and media of aorta. Methods and resultsThirty-two pigs were divided into three groups: CD for 12 months; HFD for 12 months; switch diet group (regression diet; RD): HFD for 9 months followed by CD for 3 months. After 12 months, RNA was isolated from aorta intima and media for nutrigenomic analyses. HFD significantly affected gene expression in intima, while RD gene expression profile was distinct from the CD group. This suggests that switch to CD is not sufficient to correct gene expression alterations induced by HFD but counteracted expression of a group of genes. HFD also affected gene expression in media and as for intima, the expression profile of media of pigs on RD differed from that of these on CD. ConclusionsThis study revealed nutrigenomic modifications induced by long-term HFD consumption on arterial intima and media. The return to CD was not sufficient to counteract the genomic effect of HFD.

Allicin ameliorates obesity comorbid depressive-like behaviors: involvement of the oxidative stress, mitochondrial function, autophagy, insulin resistance and NOX/Nrf2 imbalance in mice.

The increased prevalence of obesity has been a major medical and public health problem in the past decades. In obese status, insulin resistance and sustained oxidative stress damage might give rise to behavioral deficits. The anti-obesity and anti-oxidant effects of allicin have been previously reported in peripheral tissues. In the present study, the functions and mechanisms of allicin involved in the prevention of high-fat diet (HFD)-induced depressive-like behaviors were investigated to better understand the pharmacological activities of allicin. Obese mice (five weeks of age) were treated with allicin (50, 100, and 200mg/kg) by gavage for 15weeks and behavioral test (sucrose preference, open field, and tail suspension) were performed. Furthermore, markers of oxidative stress, mitochondrial function, autophagy, and insulin resistance were measured in the hippocampal tissue. Finally, the levels of NADPH oxidase (NOX2, NOX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were evaluated in the hippocampus. The body weight, metabolic disorders, and depressive-like behaviors in obese mice were ameliorated by allicin. The depressive-like behaviors presented in the obese mice were accompanied by remarkably excessive reactive oxygen species (ROS) production and oxidative stress, damaged mitochondrial function, imbalanced autophagy, and enhanced insulin resistance in the hippocampus. We found that allicin improved the above undesirable effects in the obese mice. Furthermore, allicin significantly decreased NOX2 and NOX4 levels and activated the Nrf2 pathway. Allicin attenuated depressive-like behaviors triggered by long-term HFD consumption by inhibiting ROS production and oxidative stress, improving mitochondrial function, regulating autophagy, and reducing insulin resistance in the hippocampus via optimization of NOX/Nrf2 imbalance.

Transcriptomic Alterations of the Aortic Intima and Media in Long-term High-fat Diet Fed Pigs and Its Reversal (P15-010-19)

ObjectivesWe have previously shown that 12 months (mo.) high-fat diet (HFD) in pigs led to pathophysiological alterations, incl. fattening and increased femoral artery intima-media-thickness, which were partly reversed after 3 mo. return to control diet (Zabek et al., PLoS One 2017). The aim of this study was to decipher underlying mechanism of action of these dietary interventions on the arteries by nutrigenomics analyses of intima and media of aorta. Methods32 female pigs were divided into 3 groups: Control diet (CD) for 12 mo; HFD for 12 mo; 3) Reversal diet group (RD): HFD for 9 mo followed by CD for 3 mo After 12 mo animals were killed and abdominal aorta collected. RNA was isolated from aorta intima and media for whole genome microarray analyses followed by bioinformatics analyses. ResultsHFD compared to CD group significantly affected gene expression profile in intima with genes belonging to the chemotaxis, inflammation or endothelial permeability. RD induced gene expression profile was distinct from the CD group. This suggests that 3 mo of reversal to CD is not sufficient to correct gene expression changes induced by HFD. Comparison of RD profile with that of HFD group revealed a group of genes with opposite expression, e.g., genes regulating inflammation, toll-like cell signaling pathway or cytoskeleton organization involved in the regulation of cell permeability. This suggests that return to the RD only partly restored gene expression alterations due to the HFD. Significant changes in expression of genes in media following HFD were also observed, such as genes involved in cytoskeleton organization and migration MAPK signaling. As for intima, the expression profile of media of pigs on RD was different on that of these on CD diet. Compared to HFD, a group of genes involved in PI3K or MAPK pathways presented opposite expression suggesting that RD can partly correct the changes in genomic effect induced by HFD. ConclusionsThis study revealed genomic modifications induced by long-term HFD consumption on arterial intima and media. The return to normal diet for 3 mo was not sufficient to counteract the genomic effect of long-term HFD consumption. Funding SourcesWROVASC Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund.

Stressing the importance of choice: Validity of a preclinical free-choice high-caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet-induced obesity and metabolic dysfunction.

Humans have engineered a dietary environment that has driven the global prevalence of obesity and several other chronic metabolic diseases to pandemic levels. To prevent or treat obesity and associated comorbidities, it is crucial that we understand how our dietary environment, especially in combination with a sedentary lifestyle and/or daily‐life stress, can dysregulate energy balance and promote the development of an obese state. Substantial mechanistic insight into the maladaptive adaptations underlying caloric overconsumption and excessive weight gain has been gained by analysing brains from rodents that were eating prefabricated nutritionally‐complete pellets of high‐fat diet (HFD). Although long‐term consumption of HFDs induces chronic metabolic diseases, including obesity, they do not model several important characteristics of the modern‐day human diet. For example, prefabricated HFDs ignore the (effects of) caloric consumption from a fluid source, do not appear to model the complex interplay in humans between stress and preference for palatable foods, and, importantly, lack any aspect of choice. Therefore, our laboratory uses an obesogenic free‐choice high‐fat high‐sucrose (fc‐HFHS) diet paradigm that provides rodents with the opportunity to choose from several diet components, varying in palatability, fluidity, texture, form and nutritive content. Here, we review recent advances in our understanding how the fc‐HFHS diet disrupts peripheral metabolic processes and produces adaptations in brain circuitries that govern homeostatic and hedonic components of energy balance. Current insight suggests that the fc‐HFHS diet has good construct and face validity to model human diet‐induced chronic metabolic diseases, including obesity, because it combines the effects of food palatability and energy density with the stimulating effects of variety and choice. We also highlight how behavioural, physiological and molecular adaptations might differ from those induced by prefabricated HFDs that lack an element of choice. Finally, the advantages and disadvantages of using the fc‐HFHS diet for preclinical studies are discussed.

Effects of oral fat stimulation on fat taste perception and preference among Japanese young men and women

Recent evidence suggests that oral chemoreception is involved in the detection of fat via its breakdown products, fatty acids. In addition, long‐term consumption of high‐fat diet was reported to decrease oral fatty acid sensitivity. However, it is unclear whether dietary fat temporarily modulates fat taste perception and preference. We examined whether dietary fat stimulation of lingual lipid sensors affects oral fatty acid sensitivity and fat preference, and compared the results with those of sucrose among healthy young Japanese men and women. In addition, we assessed the sex difference or effects of sex hormones on the basal level of oral fatty acid sensitivity, fat preference, and changes in their levels after dietary fat stimulation.Female subjects participated in laboratory experiments three times in a random order in the early and late follicular phases, and mid‐luteal phases during the menstrual cycle, and male subjects did so on an arbitrary day. To test oral fatty acid sensitivity, oleic acid (C18:1) detection thresholds were determined using a three‐alternative forced‐choice methodology. The fat preference test was carried out by choosing the preference for cottage cheese containing four different concentrations of food lipids. Measurements of oleic acid detection threshold and fat preference were repeated after a lingual stimulation by 5 min exposure of dietary fat or sucrose. After the experiments, subjects consumed a buffet‐style lunch where they ate various food items until comfortably full, and their energy intake, fat intake, and fat‐energy ratio was assessed. We analyzed the relationship between oleic acid sensitivity and fat preference, or energy intake and the effects of sex hormones on these variables.Oral oleic acid thresholds did not vary between men and women in the early follicular phase, but changed in three phases during the menstrual cycle in women. Short‐term lingual stimulation with dietary fat enhanced the oleic acid thresholds in both women and men. In addition, there was a correlation between the oleic acid threshold and energy intake after the stimulation. The present result suggests that oral fatty acid sensitivity decreases after dietary fat stimulation and mediates total energy intake in a meal. Additionally, ovarian hormones possibly affect energy intake through oral fatty acid sensitivity in women.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term consumption of high-fat diet impairs motor coordination without affecting the general motor activity

Long-term consumption of high-fat diet impairs motor coordination without affecting the general motor activity

The effects of ovariectomy and lifelong high-fat diet consumption on body weight, appetite, and lifespan in female rats

In females, ovarian hormones play pivotal roles in metabolic, appetite, and body weight regulation. In addition, it has been reported that ovarian hormones also affect longevity in some species. Recently, it was found that the consumption of a high-fat diet aggravates ovariectomy-associated metabolic dysregulation in female rodents. The aim of this study was to investigate the hypothesis that long-term high-fat diet consumption and ovariectomy interact to worsen body weight regulation and longevity in female rats.At 21days of age, female rats were weaned and randomly divided into two groups, one of which was given the high-fat diet, and the other was supplied with standard chow. At 23weeks of age, each group was further divided into ovariectomized and sham-operated groups, and then their body weight changes, food intake, and longevity were measured until 34months of age. The sham – high-fat diet rats exhibited greater body weight changes and higher feed efficiency than the sham – standard chow rats. On the other hand, the ovariectomized – high-fat diet and ovariectomized - standard chow rats displayed similar body weight changes and feed efficiency. The sham – high-fat diet and ovariectomized – standard chow rats demonstrated similar body weight changes and feed efficiency, indicating that the impact of ovariectomy on the regulation of body weight and energy metabolism might be similar to that of high-fat diet. Contrary to our expectations, ovariectomy and high-fat diet consumption both had small favorable effects on longevity. As the high-fat diet used in the present study not only had a high fat content, but also had a high caloric content and a low carbohydrate content compared with the standard chow, it is possible that the effects of the high-fat diet on body weight and longevity were partially induced by its caloric/carbohydrate contents. These findings indicate that the alterations in body weight and energy metabolism induced by ovariectomy and high-fat diet might not directly affect the lifespan of female rats.