scholarly journals Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5279
Author(s):  
Macarena González-Portilla ◽  
Sandra Montagud-Romero ◽  
Francisco Navarrete ◽  
Ani Gasparyan ◽  
Jorge Manzanares ◽  
...  

Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.

2021 ◽  
pp. 1-14
Author(s):  
Jian Bao ◽  
Zheng Liang ◽  
Xiaokang Gong ◽  
Jing Yu ◽  
Yifan Xiao ◽  
...  

Background: 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. Objective: The objective of this study was to explore the underlying neurobiological mechanisms of HFD influenced Aβ accumulation and cognitive performance during AD pathology. Methods: 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. Results: 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. Conclusion: 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.


Author(s):  
Yun Gi Kim ◽  
Kyung-Do Han ◽  
Jong-Il Choi ◽  
Ki Yung Boo ◽  
Do Young Kim ◽  
...  

Abstract Aims Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking. Methods and results A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916–0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373–1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF. Conclusion Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF.


2007 ◽  
Vol 293 (1) ◽  
pp. E121-E131 ◽  
Author(s):  
Michelle Lee ◽  
Andrea Kim ◽  
Streamson C. Chua ◽  
Silvana Obici ◽  
Sharon L. Wardlaw

To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH2-terminal POMC transgene that includes α- and γ3-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD ( P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD ( P < 0.05) and were more pronounced on HFD ( P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD ( P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences.


2018 ◽  
Author(s):  
Susanna Søberg ◽  
Emilie S. Andersen ◽  
Niels B. Dalgaard ◽  
Ida Jarlhelt ◽  
Nina L. Hansen ◽  
...  

ABSTRACTObjectiveExcessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence adlibitumalcohol intake may be incomplete. Two large studies recently linked variants in theKLBlocus with levels of alcohol intake in humans.KLBencodes ß-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and humanFgf21variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain.MethodsWe recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma. In addition, we measured circulating FGF21 (1-181) levels, liver stiffness, triglyceride, and other metabolic parameters in three healthy Danish men before and after consuming an average of 22.6 beers/person/day (4.4 g/kg/day of ethanol) for three days during Oktoberfest 2017 in Munich, Germany. We further correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on adlibitumalcohol intake in mice.ResultsWe show that alcohol ingestion (25.3 grams or ~2.5 standard drinks) acutely increases plasma levels of FGF21 (1-181) 3.4-fold in fasting humans. We also find that binge drinking for three days at Oktoberfest is associated with a 2.1-fold increase in baseline FGF21 (1-181) levels, in contrast to minor deteriorations in metabolic and hepatic biomarkers. However, basal FGF21 (1-181) levels were not correlated with differences in alcohol-related behaviors, emotional responses, or problems in our non-alcoholic subjects. Finally, we show that once-daily injection of recombinant human FGF21 reduces adlibitumalcohol intake by 21% in mice.ConclusionsFGF21 (1-181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol intake in mice. These observations are consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Daiane Figueiredo Rosa ◽  
Mariáurea Matias Sarandy ◽  
Rômulo Dias Novaes ◽  
Mariella Bontempo Freitas ◽  
Maria do Carmo Gouveia Pelúzio ◽  
...  

The wound-healing process is complex and remains a challenging process under the influence of several factors, including eating habits. As improper diets may lead to disorders such as dyslipidemia, insulin resistance, and chronic inflammation, potentially affecting the tissue ability to heal, we decided to investigate the effect of a high-fat diet and alcohol intake on the inflammatory process and skin wound healing in Wistar rats. Male rats (n=30) were individually housed in cages with food and water ad libitum (registration number 213/2014). After anesthesia, at day 40, three circular wounds (12 mm diameter) were made on the back of each animal, which were then randomly assorted into five treatment groups: C1 (control 1)—water via gavage and standard chow diet; C2 (control 2)—water (no gavage) and standard chow diet; AL (alcohol)—water (no gavage) and alcohol (40%) via gavage and standard chow diet; HF (high fat)—water (no gavage) and high-fat diet (50%); and HF + AL (alcohol/high fat)—water (no gavage), alcohol (40%) via gavage, and high-fat diet. Animals were treated for 61 days. Every seven days, the area and the rate of wound contraction were evaluated. Tissue samples were removed for histopathological analysis and biochemical analyses. Our results showed that wound contraction was not complete in the HF + AL rats. Two specific indices of wound-healing impairment (total cell number and levels of the inflammatory cytokine TGF-β) were increased in the HF + AL rats. We also observed decreased type I and III collagen fibers in the HF, AL, and HF + AL groups and increased oxidative stress markers in the same groups. We suggest that a high-fat diet combined with alcohol intake contributed to delayed skin wound healing through increase of the inflammatory phase and promoting oxidative stress, which may have led to morphological alterations and impaired matrix remodeling.


2020 ◽  
Vol 55 (2) ◽  
pp. 225-232
Author(s):  
Louise Katrine Kjaer Weile ◽  
Chunsen Wu ◽  
Hanne Kristine Hegaard ◽  
Ulrik Schiøler Kesmodel ◽  
Tine Brink Henriksen ◽  
...  

Abstract Aims This study aimed to examine the feasibility of a web-based questionnaire when collecting information on alcohol consumption in pregnancy to identify women with risk drinking behaviour, and to describe factors associated with risk drinking behaviour, and the use of specialized care for prenatal risk drinking. Methods In 2413 women referred to antenatal care at Odense University Hospital, Denmark, April–October 2018, self-reported alcohol intake was retrieved from a web-based questionnaire. Replies were screened for risk drinking behaviour: current intake of ≥7 drinks/week, ≥3 binge drinking episodes (intake of ≥5 drinks on a single occasion) in pregnancy, binge drinking after recognition of pregnancy and/or a TWEAK-score ≥ 2 points. Women with risk drinking behaviour were called to clarify the need for specialized care. A summary of the interview was obtained from the medical records. Results Overall, 2168 (90%) completed the questionnaire. Of 2097 women providing information on alcohol intake, 77 (4%) had risk drinking behaviour. Risk drinking was associated with higher alcohol intake prior to pregnancy, spontaneous conception, younger age, nulliparity and higher level of physical activity in pregnancy. Amongst 47 women with risk drinking behaviour reached by phone, five (11%, 95% CI 4–23%) accepted examinations of the child by paediatrician and child psychologist, and &lt;3 (not further specified due to small numbers) were referred to specialized antenatal care. Conclusions A web-based questionnaire was feasible when collecting information on alcohol consumption in pregnancy to identify risk drinking behaviour. Women with risk drinking behaviour had a low acceptance of referral to specialized care.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katrina Han ◽  
Dominic Nicholas Reeds ◽  
Julia Passyn Dunn

Abstract BACKGROUNDThe effects of alcohol intake on insulin sensitivity have produced conflicting results with both beneficial and adverse effects observed. This study aimed to compare the relationship between patterns of alcohol consumption and insulin sensitivity in obese Veterans. METHODSWe performed a cross-sectional study of obese (BMI 30.0-45.0 kg/m2), nondiabetic U.S. Military Veterans without active mental health diagnoses, including no report of dependent alcohol use within the last 12 months. Alcohol exposure over the previous 12 months (mos) was assessed using a study-developed questionnaire and Michigan Alcoholism Screening Test (MAST). Fasting insulin, glucose, and a 75gm OGTT were completed to determine Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and prediabetes (preDM) score of 0, 1, or 2 based on fulfilling 0, 1, or at least 2 of the ADA criteria for preDM, respectively. Linear regression was used to assess for associations between measures of insulin resistance and alcohol consumption; unstandardized β and p-value are reported for variable of interest. RESULTS104 Veterans participated (66% males; 44±8years (range: 25-60); BMI 36±4kg/m2 (range: 29-45); 53% White, 46% African American, 2% Alaskan/Native American, 1% Other). 83 participants reported any alcohol intake in the previous 12 mos and neither preDM score (p=0.57) nor HOMA-IR (p=0.14) were predicted by this question. PreDM score groups were similar in gender, BMI, and weight, but age predicted both preDM score (r2=0.09, β=0.025, p=0.006) and HOMA-IR (r2=0.05, β=-0.09, p=0.034); therefore, all regressions were adjusted for age. There was a negative association between the number of days of alcohol intake with HOMA-IR (β=-0.271, p=0.037) but no association occurred with preDM score (p=0.15). Fewer days of binge drinking was associated with higher HOMA-IR (β= -0.342, p=0.058) and preDM score (β=-0.075, p=0.05). There was no significant association between total quantity of alcohol intake and HOMA-IR (p=0.13) nor preDM score (p=0.15). There was no association between MAST score and HOMA-IR (p=0.7) or preDM score (p=0.3). CONCLUSIONIn our cohort of obese, non-alcohol dependent Veterans, the reported number of days of alcohol intake and days of binge drinking in the previous 12 mos were lower in those with markers of insulin resistance. These results suggest that drinking patterns among obese patients may have unique effects on insulin sensitivity that warrant further investigation.


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