Applying behavioral economics-based approaches to examine the effects of liquid sucrose consumption on motivation.

Overconsumption of sugar contributes to obesity in part by changing the activity of brain areas that drive the motivation to seek out and consume food. Sugar-sweetened beverages are the most common source of excess dietary sugar and contribute to weight gain. However, very few studies have assessed the effects of liquid sucrose consumption on motivation. This is due in part to the need for novel approaches to assess motivation in pre-clinical models. To address this, we developed a within-session behavioral economics procedure to assess motivation for liquid sucrose. We first established and validated the procedure: we tested several sucrose concentrations, evaluated sensitivity of the procedure to satiety, and optimized several testing parameters. We then applied this new procedure to determine how intermittent vs. continuous access to liquid sucrose (1 M) in the home cage affects sucrose motivation. We found that intermittent liquid sucrose access results in an escalation of sucrose intake in the home cage, without altering motivation for liquid sucrose during demand testing (1 M or 0.25 M) compared to water-maintained controls. In contrast, continuous home cage access selectively blunted motivation for 1 M sucrose, while motivation for 0.25 M sucrose was similar to intermittent sucrose and control groups. Thus, effects of continuous home cage liquid sucrose access were selective to the familiar sucrose concentration. Finally, effects of sucrose on motivation recovered after removal of liquid sucrose from the diet. These data provide a new approach to examine motivation for liquid sucrose and show that escalation of intake and motivation for sucrose are dissociable processes.

High sucrose diet does not impact spatial cognition in rats using advanced touchscreen technology.

INTRODUCTION: Western diets, including those consisting of saturated fats, simple sugars and processed foods, is rising at an unprecedented rate. These lead to obesity and metabolic diseases, and possibly cognitive deficits. Exploring this, recent studies demonstrate marked impairment in spatial learning in rodents exposed to high-sugar diets. We utilised advanced touchscreen technology to assess several spatial and non-spatial components of cognition in rats chronically exposed to a high sucrose diet. METHODS: Male Wistar rats received 70 ml of 10% sucrose solution each day, or control tap water, persisting for the experiment duration (total n = 32). After 5 weeks of diet, rats performed Pairwise Discrimination, Location Discrimination, or Progressive Ratio tasks on automated touchscreens, and performance compared between groups. RESULTS: Sucrose rats consumed all the sugar solution provided to them, and had significantly increased caloric intake, compared to controls (p < 0.0001). However, in all tests, we found no significant difference in cognitive performance between Sucrose and Control treated rats. This included the number of trials for acquisition, and reversal, in Pairwise Discrimination, and number of trials required to complete Location Discrimination (p > 0.05 for all outcomes). No differences were observed in perseverative behaviour, motivation levels, or processing speed. CONCLUSION: Our study found no evidence to suggest that chronic consumption of sucrose impairs cognition, including both spatial and non-spatial learning tasks. These findings suggest that not all aspects of spatial cognition are negatively impacted by high sugar diet in rodents, and that particular use of touchscreen technology may probe different aspects of cognition than traditional tasks.

Assessment of Glycemic Response to Model Breakfasts Varying in Glycemic Index (GI) in 5-7-Year-Old School Children.

Reduced Glycemic Index (GI) of breakfast has been linked to improved cognitive performance in both children and adult populations across the morning. However, few studies have profiled the post-prandial glycemic response (PPGR) in younger children. The aim of this study was to assess PPGR to breakfast interventions differing in GI in healthy children aged 5-7 years. Eleven subjects completed an open-label, randomized, cross-over trial, receiving three equicaloric test beverages (260 kcal) consisting of 125 mL semi-skimmed milk and 50 g sugar (either glucose, sucrose, or isomaltulose). On a fourth occasion, the sucrose beverage was delivered as intermittent supply. PPGR was measured over 180 min using Continuous Glucose Monitoring (CGM). The incremental area under the curve (3h-iAUC) was highest for the glucose beverage, followed by intermittent sucrose (-21%, p = 0.288), sucrose (-27%, p = 0.139), and isomaltulose (-48%, p = 0.018). The isomaltulose beverage induced the smallest Cmax (7.8 mmol/L vs. >9.2 mmol/L for others) and the longest duration with moderate glucose level, between baseline value and 7.8 mmol/L (150 vs. <115 min for others). These results confirm that substituting mid-high GI sugars (e.g., sucrose and glucose) with low GI sugars (e.g., isomaltulose) during breakfast are a viable strategy for sustained energy release and glycemic response during the morning even in younger children.

Solanum anguivi Lam. fruit preparations counteract the negative effects of a high-sugar diet on the glucose metabolism in Drosophila melanogaster.

Solanum anguivi Lam. fruits (SALF) are traditionally consumed as a remedy for type 2 diabetes mellitus (T2DM). However, data regarding the potential anti-diabetic effect of SALF and its underlying mechanisms are scarce. As the fruit fly's energy metabolism has been suggested to be comparable with mammals including the secretion of insulin-like peptides, we fed Drosophila melanogaster a high-sugar diet (HSD) to induce a T2DM-like phenotype and subsequently exposed them to a HSD supplemented with SALF. Following, flies were analyzed for various biomarkers in relation to energy metabolism. The HSD-induced glucose levels were significantly down-regulated in flies exposed to a HSD supplemented with SALF. In addition, flies exposed to SALF-supplemented HSD exhibited a better survival in comparison to HSD-fed counterparts. Other parameters of the energy metabolism such as triglyceride levels, weights, and fitness were not affected by SALF supplementation. This was also true for the expression levels of the insulin-like-peptides 3 and 6 as well as for spargel, the Drosophila homolog of PPARγ-co-activator 1α, a central player in mitochondrial biogenesis. Overall, the present study shows that SALF significantly lowered the HSD-induced glucose levels and increased the survival while the biomarkers of the energy metabolism were not affected.

Coherent theta activity in the medial and orbital frontal cortices encodes reward value.

This study examined how the medial frontal (MFC) and orbital frontal (OFC) cortices process reward information. We simultaneously recorded local field potentials in the two areas as rats consumed liquid sucrose rewards. Both areas exhibited a 4-8 Hz 'theta' rhythm that was phase-locked to the lick cycle. The rhythm tracked shifts in sucrose concentrations and fluid volumes, demonstrating that it is sensitive to differences in reward magnitude. The coupling between the rhythm and licking was stronger in MFC than OFC and varied with response vigor and absolute reward value in the MFC. Spectral analysis revealed zero-lag coherence between the cortical areas, and found evidence for a directionality of the rhythm, with MFC leading OFC. Our findings suggest that consummatory behavior generates simultaneous theta range activity in the MFC and OFC that encodes the value of consumed fluids, with the MFC having a top-down role in the control of consumption.

Distinct Impact of Natural Sugars from Fruit Juices and Added Sugars on Caloric Intake, Body Weight, Glycaemia, Oxidative Stress and Glycation in Diabetic Rats.

Although fruit juices are a natural source of sugars, there is a controversy whether their sugar content has similar harmful effects as beverages' added-sugars. We aimed to study the role of fruit juice sugars in inducing overweight, hyperglycaemia, glycation and oxidative stress in normal and diabetic animal models. In diabetic Goto-Kakizaki (GK) rats, we compared the effects of four different fruit juices (4-weeks) with sugary solutions having a similar sugar profile and concentration. In vitro, the sugary solutions were more susceptible to AGE formation than fruit juices, also causing higher postprandial glycaemia and lower erythrocytes' antioxidant capacity in vivo (single intake). In GK rats, ad libitum fruit juice consumption (4-weeks) did not change body weight, glycaemia, oxidative stress nor glycation. Consumption of a matched volume of sugary solutions aggravated fasting glycaemia but had a moderate impact on caloric intake and oxidative stress/glycation markers in tissues of diabetic rats. Ad libitum availability of the same sugary solutions impaired energy balance regulation, leading to higher caloric intake than ad libitum fruit juices and controls, as well as weight gain, fasting hyperglycaemia, insulin intolerance and impaired oxidative stress/glycation markers in several tissues. We demonstrated the distinct role of sugars naturally present in fruit juices and added sugars in energy balance regulation, impairing oxidative stress, glycation and glucose metabolism in an animal model of type 2 diabetes.

Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human-Like Bile Acid Composition.

Western-style high-fat/high-sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD-induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild-type (WT) and human-like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography-tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD-induced change of gut microbiota inhibited BA deconjugation and 7α-dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human-like hydrophobic BA composition.

Sex- and age-dependent outcomes of 9-hour time-restricted feeding of a Western high-fat high-sucrose diet in C57BL/6J mice.

Time-restricted feeding (TRF) is a nutritional intervention wherein food intake is limited to a consistent 8- to 10-h daily window without changes in nutritional quality or quantity. TRF can prevent and treat diet-induced obesity (DIO) and associated metabolic disease in young male mice fed an obesogenic diet, the gold standard preclinical model for metabolic disease research. Because age and sex are key biological variables affecting metabolic disease pathophysiology and response to therapies, we assessed their impact on TRF benefits by subjecting young 3-month-old or middle-aged 12-month-old male and female mice to ad libitum or TRF of a Western diet. We show that most of the benefits of TRF are age-independent but are sex-dependent. TRF protects both sexes against fatty liver and glucose intolerance while body weight benefits are observed only in males. We also find that TRF imparts performance benefits and increases survival to sepsis in both sexes.

A pilot feasibility study investigating the impact of increasing sucrose intakes on body composition and blood pressure.

Epidemiological and intervention studies have reported negative health effects of sucrose intake, but many of these studies were not representative of typical dietary habits. In this pilot study, we aimed to test the effect of increasing sucrose intakes for 1 week on body composition and blood pressure and explore the feasibility of consuming high intakes of sucrose in addition to a habitual diet. In a randomised crossover design study, twelve healthy participants (50 % female, age 28⋅4 ± 10 years, BMI 25 ± 3 kg/m2), consumed either 40, 80 or 120 g sucrose in 500 ml water in addition to their habitual diet every day for 1 week, with a 1-week washout between treatment periods. Body composition (assessed using bioelectrical impedance) and blood pressure measurements were taken before and after each intervention phase. All participants reported no issues with consuming the sucrose dose for the intervention period. There was a significant increase in systolic blood pressure following 120 g sucrose intake (P = 0⋅006), however there was no significant changes to blood pressure, body weight, BMI, percentage protein, fat or water (P > 0⋅05) when comparing change from baseline values. There was also no effect of sucrose intakes on energy or macronutrient intakes during the intervention (P > 0⋅05). We show here that varying doses of sucrose over a 1-week period have no effect on body composition or blood pressure. The amounts of sucrose used were an acceptable addition to the habitual diet and demonstrate the feasibility of larger-scale studies of chronic sucrose supplementation.

Improvement Effect of Sweet Basil (Ocimum basilicum L.) Powder Intake on Obese Mice Fed a High-fat and High-sucrose Diet.

This study aimed to determine if there are anti-inflammatory and anti-obesity effects of sweet basil, an herb, in mice. Sweet basil was administered as a powder to male C57BL/6JJcl mice, which were divided into three groups: the (control [C], high-fat and high-sucrose diet [H], and high-fat and high-sucrose diet plus sweet basil powder [HB]) groups. The mice were fed for 12 weeks and the dry sweet basil powder comprised 1% per kg of the diet. From experiment third week, the average body weight was significantly higher in the H group than in the C group. The average body weight was significantly lower in the HB group than in the H group, but food intake did not significantly differ between the H and HB groups. Liver weight was drastically lower in the HB group than in the H group. Perirenal fat weight and epididymal fat weight were not significantly different between the H and HB groups. Therefore, we assumed that body-weight reduction caused by sweet basil powder intake depended on inhibition of liver enlargement. We then examined lipid metabolism-related gene expression in the mice livers. Expression of the sterol response element binding protein 1-c gene tended to be lower in the HB group than in the H group (p=0.056). We speculated that sweet basil inhibited liver enlargement by suppressing fatty acid synthesis. Moreover, expression of the monocyte chemoattractant protein-1 gene in epididymal fat was significantly lower in the HB group than in the H group. Sweet basil powder appears to have a potent anti-inflammatory effect in the adipose tissue of mice fed a high-fat and high-sucrose diet.

AB-Kefir Reduced Body Weight and Ameliorated Inflammation in Adipose Tissue of Obese Mice Fed a High-Fat Diet, but Not a High-Sucrose Diet.

Consumption of different types of high-calorie foods leads to the development of various metabolic disorders. However, the effects of multi-strain probiotics on different types of diet-induced obesity and intestinal dysbiosis remain unclear. In this study, mice were fed a control diet, high-fat diet (HFD; 60% kcal fat and 20% kcal carbohydrate), or western diet (WD; 40% kcal fat and 43% kcal carbohydrate) and administered with multi-strain AB-Kefir containing six strains of lactic acid bacteria and a Bifidobacterium strain, at 109 CFU per mouse for 10 weeks. Results demonstrated that AB-Kefir reduced body weight gain, glucose intolerance, and hepatic steatosis with a minor influence on gut microbiota composition in HFD-fed mice, but not in WD-fed mice. In addition, AB-Kefir significantly reduced the weight and size of adipose tissues by regulating the expression of CD36, Igf1, and Pgc1 in HFD-fed mice. Although AB-Kefir did not reduce the volume of white adipose tissue, it markedly regulated CD36, Dgat1 and Mogat1 mRNA expression. Moreover, the abundance of Eubacterium_coprostanoligenes_group and Ruminiclostridium significantly correlated with changes in body weight, liver weight, and fasting glucose in test mice. Overall, this study provides important evidence to understand the interactions between probiotics, gut microbiota, and diet in obesity treatment.

Habitual Dietary Intake Affects the Altered Pattern of Gut Microbiome by Acarbose in Patients with Type 2 Diabetes.

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.

Prolonged Chronic Consumption of a High Fat with Sucrose Diet Alters the Morphology of the Small Intestine.

(1) The high-fat diet (HFD) of western countries has dramatic effect on the health of several organs, including the digestive tract, leading to the accumulation of fats that can also trigger a chronic inflammatory process, such as that which occurs in non-alcohol steatohepatitis. The effects of a HFD on the small intestine, the organ involved in the absorption of this class of nutrients, are still poorly investigated. (2) To address this aspect, we administered a combined HFD with sucrose (HFD w/Suc, fat: 58% Kcal) regimen (18 months) to mice and investigated the morphological and molecular changes that occurred in the wall of proximal tract of the small intestine compared to the intestine of mice fed with a standard diet (SD) (fat: 18% Kcal). (3) We found an accumulation of lipid droplets in the mucosa of HFD w/Suc-fed mice that led to a disarrangement of mucosa architecture. Furthermore, we assessed the expression of several key players involved in lipid metabolism and inflammation, such as perilipin, leptin, leptin receptor, PI3K, p-mTOR, p-Akt, and TNF-α. All these molecules were increased in HFD mice compared to the SD group. We also evaluated anti-inflammatory molecules like adiponectin, adiponectin receptor, and PPAR-γ, and observed their significant reduction in the HFD w/Suc group compared to the control. Our data are in line with the knowledge that improper eating habits present a primary harmful assault on the bowel and the entire body's health. (4) These results represent a promising starting point for future studies, helping to better understand the complex and not fully elucidated spectrum of intestinal alterations induced by the overconsumption of fat.

Contractility of permeabilized rat vastus intermedius muscle fibres following high-fat, high-sucrose diet consumption.

Obesity is a worldwide health concern associated with impaired physical function. It is not clear if contractile protein dysfunction contributes to the impairment of muscle function observed with obesity. The purpose of this study was to examine if diet-induced obesity affects contractile function of chemically permeabilized vastus intermedius fibres of male Sprague-Dawley rats expressing fast myosin heavy chain (MHC) IIa or slow MHC I. Rats consumed either a high-fat, high sucrose (HFHS) diet or a standard (CHOW) diet beginning as either weanlings (7-week duration: WEAN7 cohort, or 14-week duration: WEAN14 cohort) or young adults (12-week duration: ADULT12 cohort, 24-week duration: ADULT24 cohort). HFHS-fed rats had higher (P < 0.05) whole-body adiposity (derived from dual-energy X-ray absorptiometry) than CHOW-fed rats in all cohorts. Relative to CHOW diet groups, the HFHS diet was associated with impaired force production in (a) MHC I fibres in the ADULT24 cohort; and (b) MHC IIa fibres in the ADULT12 and ADULT24 cohorts combined. However, the HFHS diet did not significantly affect the Ca2+-sensitivity of force production, unloaded shortening velocity, or ratio of active force to active stiffness in any cohort. We conclude that diet-induced obesity can impair force output of permeabilized muscle fibres of adult rats. Novelty: We assessed contractile function of permeabilized skeletal muscle fibres in a rat model of diet-induced obesity. The high-fat, high-sucrose diet was associated with impaired force output of fibres expressing MHC I or MHC IIa in some cohorts of rats. Other measures of contractile function were not significantly affected by diet.

Saskatoon berry powder reduces hepatic steatosis and insulin resistance in high fat-high sucrose diet-induced obese mice.

Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.

The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study.

OBJECTIVE: To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain. METHODS: In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed. Differences in fMRI signals between views of low-fat (LF (<30%)) high sugar (HS (>30%)) food, and non-food images were calculated in brain regions implicated in energy homeostasis, taste, and reward. RESULTS: All participants in the SSB (6F 4M; 8 Caucasian; 36±14 y, 28.2±5.5 kg/m2; Mean±SD) and SSS (3F 7M; 6 Caucasian; 39±12; 26.3±4.4) groups completed the study. Weight change was 0.27±0.78 kg between SSB and SSS participants. Changes in the fMRI response to LF/HS foods in reward, homeostatic and taste regions tended to not be different between the groups over the four weeks. However, activation of the right substantia nigra increased following the SSB but decreased activation following the SSS in response to LF/HS foods over 28 days (-0.32±0.12). Ratings of wanting for LF/HS foods were correlated with activation in several brain regions, including the OFC. CONCLUSIONS: Change in weight was modest between the groups in this study. Daily consumption of a SSB over 28 days led to mixed responses to LF/HS foods in areas of the brain associated with reward. Ratings of wanting are correlated with fMRI activation inside an MRI scanner.

Effects of two different doses of carbohydrate ingestion on taekwondo-related performance during a simulated tournament.

BACKGROUND: Carbohydrate (CHO) ingestion enhances exercise performance; however, the efficacy of CHO intake on repeated bouts of exercise simulating a taekwondo tournament is unknown. Therefore, the purpose was to compare the effects of two different doses of CHO on a sports-specific kicking test during a simulated taekwondo tournament compared to placebo (PLA). METHODS: In a double-blind, randomized-placebo controlled, cross-over trial, eleven junior male professional taekwondo athletes (age: 16 ± 0.8 years, body mass: 55.3 ± 7.3 kg) ingested one of three solutions: (i) high dose (C45): 45 g of CHO (60 g∙h- 1), (ii) low dose (C22.5): 22.5 g of CHO (30 g∙h- 1; both solutions containing 2:1 glucose:fructose), or a PLA immediately following each kicking test. The kicking test was repeated 5 times, separated by 45 mins of rest, simulating a typical taekwondo competition day. Ratings of perceived exertion (RPE) and gastrointestinal discomfort (GI) scores were collected immediately after, and blood glucose before each test. RESULTS: The results revealed that C45 and C22.5 did not improve total, successful, or percentage of successful kicks compared to PLA (p > 0.05). Blood glucose was significantly higher following both CHO conditions compared with PLA across all five tests (p < 0.05). There were no differences between treatments or across tests for RPE (p > 0.05). CONCLUSION: CHO intake, independent of the dose, did not alter taekwondo kick performance during a simulated taekwondo tournament.

Dietary obesity in mice is associated with lipid deposition and metabolic shifts in the lungs sharing features with the liver.

Obesity is associated with both chronic and acute respiratory illnesses, such as asthma, chronic obstructive pulmonary disease (COPD) or increased susceptibility to infectious diseases. Anatomical but also systemic and local metabolic alterations are proposed contributors to the pathophysiology of lung diseases in the context of obesity. To bring perspective to this discussion, we used NMR to compare the obesity-associated metabolomic profiles of the lung with those of the liver, heart, skeletal muscles, kidneys, brain and serum from male C57Bl/6J mice fed with a high-fat and high-sucrose (HFHSD) diet vs. standard (SD) chow for 14 weeks. Our results showed that the lung was the second most affected organ after the liver, and that the two organs shared reduced one-carbon (1C) metabolism and increased lipid accumulation. Altered 1C metabolism was found in all organs and in the serum, but serine levels were increased only in the lung of HFHSD compared to SD. Lastly, tricarboxylic acid (TCA)-derived metabolites were specifically and oppositely regulated in the serum and kidneys but not in other organs. Collectively, our data highlighted that HFHSD induced specific metabolic changes in all organs, the lung being the second most affected organ, the main alterations affecting metabolite concentrations of the 1C pathway and, to a minor extend, TCA. The absolute metabolite quantification performed in this study reveals some metabolic specificities affecting both the liver and the lung, that may reveal common metabolic determinants to the ongoing pathological process.

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis.

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.