Effect Of Dietary Fat Content Research Articles

The Effects of Dietary Fat Content and Triacylglycerol Structures on the Vitamin A Storage in Mice

ObjectivesVitamin A (VA, retinol) is a fat-soluble micronutrient that plays a variety of physiological functions form development to metabolism in humans and animals. The VA metabolism and storage can be affected by many different factors and high fat diet is one of them. As a major dietary lipid component, elevations of dietary intake of triacylglycerol (TAG) are associated with a variety of metabolic abnormalities. The alternation of TAG structure can change its physicochemical features or physiological impacts. We hypothesis that the structure of TAG fatty acyl position may affect the absorption and metabolism of VA in animal body.MethodsTwenty-seven 6-week-old male C57/BL6J mice at 6 weeks of age were randomly assigned to 3 dietary treatment groups, 1,2-dipalmitoyl-3-oleoylglycerol (PPO, 36% w/w chow diet), 1,3-dipalmitoyl-2-oleoylglycerol (POP, 36% w/w chow diet), and the chow diet control. Mice were fed with assigned diet; their food intake and body weight were measured and record daily. At the end of six-weeks treatment, mice were sacrificed, and liver tissue were collected. Dietary Vitamin A intake for each mouse was calculated based on their food intake and vitamin A content in the chow diet. Vitamin A storage in liver was determined by high performance liquid chromatography.ResultsThe PPO and POP diets have less VA per unit due to the presence of 36% of pure TAG, which diluted the VA content in the basal chew diet. Mice fed the chew diet had significantly higher VA intake after the adjustment of total net food intake, which is associated with higher usage and storage in the chow fed group than the PPO and POP. The mice in the PPO group have significantly higher VA intake, VA storage in the liver and VA usage than those in the POP group. However, the intake/storage ratio between two high fat diet group is not different.ConclusionsThe VA usage and storage amount are associated with its dietary intakes. The feeding of a high-fat diet reduces the usage of VA due to lowered amounts of VA intakes. The TAG structure can impact the VA intakes because of TAG on metabolism in mice fed a high-fat diet.Funding SourcesThe experiment was conducted at the University of Tennessee, PI Guoxun Chen (Nutrition science) and co-PI Toni Wang (Food Science).

Sex, Dietary pH, and Protein‐dependent effects in Diet‐induced Obese Mice

Western diets, characterized by lower amounts of fruits, vegetables and lean proteins compared to higher quantities of saturated fats, fatty meats and sugar sweetened foods and beverages, have been implicated in metabolic diseases (e.g., obesity), in part, through low‐grade metabolic acidosis. Hence, the purpose of this study was to assess the effects of pH‐enhanced diets rich in beef or casein in diet induced obese B6 mice, compared to low fat‐fed mice. We hypothesized that metabolic health will be improved by consuming a diet containing pH‐enhanced cooked ground beef or casein, compared to a non pH‐enhanced beef or casein diets.Male and female mice were randomized (n=10) into 8 groups by protein source (beef protein or casein); fat content (low fat (LF) or high fat (HF)), and with or without pH‐enhancement with ammonia (N): LF casein (LFC) or LFCN; LF beef (LFB) or LFBN; HFC or HFCN; HFB, or HFBN. Weight gain and food intake were measured weekly (for 12 weeks); body composition was measured at weeks 7, 11; and glucose tolerance test (GTT) was performed at week 10.Body weight was significantly higher in all male HF groups (HF, HFN, HFB and HFBN: regardless of the protein source) compared to low fat groups (LFC, LFN, LFB, LFBN) except for the LFB group; however, no significant differences were observed in females. Male mice (but not females) fed lean beef (LFB, LFBN) exhibited significantly lower fat mass compared to mice fed HF diets with or without beef (HFC, HFB). Moreover, a significant main effect was observed for dietary fat (LF vs HF), protein source (casein vs beef) and pH (pH enhanced (N) vs not enhanced) in males’ fat mass, whereas females demonstrated a significant main effect for dietary fat (LF vs HF) but not for pH or protein source. Additionally, glucose clearance was increased (p=0.05) in LF groups compared to HF groups for both male and females. Interestingly, pH enhanced groups (HFN and HFBN) demonstrated higher glucose clearance (p=0.05) compared to HF group in both male and female mice. Surprisingly, glucose clearance was not improved by pH enhancement in the LFN group with trends towards worsening glucose intolerance (p value 0.08), compared to LF casein groups in both male and female mice. While there were differences in main effects and interactions among diet, protein source and pH enhancement in males compared to females, a significant (p=0.0001) main effect was observed in all parameters (fat mass, lean mass, final body weight, glucose clearance and serum insulin and leptin levels) among males and female mice, further confirming the sex‐dependent impact on metabolism regardless of the diet, protein source or the whether the diet pH is enhanced or not.Our findings suggest potential metabolic benefits of increasing dietary pH, as indicated by improved glucose clearance. The main effects and interactions observed in diet and protein source further indicate that it may be the amount of fat rather than the protein source, which contributes to metabolic dysfunctions. Additional research is warranted to determine sex dependent mechanisms underlying the metabolic effects of dietary fat content, protein source and interactions with dietary pH.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial

BackgroundAround 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes – abstinence for alcoholic and cholecystectomy for biliary pancreatitis – the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended.Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. Methods, designParticipants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a ‘reduced fat diet’ (15% fat, 65% carbohydrate, 20% protein) and a ‘standard healthy diet’ (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DiscussionThis study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

The effect of dietary fat content on the recurrence of pancreatitis – pre-study protocol of the effort-randomized controlled trial

The effect of dietary fat content on the recurrence of pancreatitis – pre-study protocol of the effort-randomized controlled trial

Effects of Dietary Vitamin B6 Restriction on Hepatic Gene Expression Profile of Non-Obese and Obese Mice.

Although vitamin B6 is contained in various foods, its deficiency is one of the most common micronutrient deficiencies worldwide. Furthermore, patients with obesity and cardiovascular disease are more likely to have suboptimal vitamin B6 status than healthy people. Therefore, we investigated the effects of dietary vitamin B6 restriction on hepatic gene expression and function in obese mice. C57BL/6J male mice were fed a low-fat (LF) or high-fat (HF) diet in combination with sufficient (7 mg pyridoxine/kg diet) or insufficient (1 mg) amounts of vitamin B6 for 16 weeks. Analysis of microarray data revealed that expressions of 4000 genes were significantly altered by the experimental diets (LF7, LF1, HF7, and HF1). The effects of dietary fat content on gene expressions were markedly greater than vitamin B6 content. Only three differentially expressed genes (DEGs) were overlapped between the LF1/LF7 and HF1/HF7 comparison. In the LF1/LF7 comparison, 54 upregulated DEGs were enriched in gene ontology (GO) terms associated with the sterol metabolic process and 54 downregulated DEGs were enriched in GO terms associated with immune response. In HF1/HF7 comparison, 26 upregulated DEGs were enriched in GO terms associated with amino acid catabolic process. High-fat consumption downregulated gene expressions associated with vitamin B6-dependent pathways. In conclusion, our data suggest that obesity may differentially regulate vitamin B6-associated metabolic pathways in the body.

The effect of dietary fat content on the recurrence of pancreatitis – Pre-study protocol of the EFFORT-randomized controlled trial

The effect of dietary fat content on the recurrence of pancreatitis – Pre-study protocol of the EFFORT-randomized controlled trial

Unconjugated and secondary bile acid profiles in response to higher-fat, lower-carbohydrate diet and associated with related gut microbiota: A 6-month randomized controlled-feeding trial

Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. The higher-fat diet resulted in an elevated concentration of total BAs (p<0.001), and unconjugated BAs (p=0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3β-DCA and taurolithocholic acid (TLCA) (p<0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r=0.31, p=0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r>0.3, p=0.02 and p=0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p=0.05). The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.

Dietary Macronutrient Composition Determines the Contribution of DGAT1 to Alcoholic Steatosis.

BackgroundThe first stage of alcoholic liver disease is hepatic steatosis. While alcohol is known to profoundly impact hepatic lipid metabolism, gaps in our knowledge remain regarding the mechanisms leading to alcohol‐induced hepatic triglyceride (TG) accumulation. As the sole enzymes catalyzing the final step in TG synthesis, diacylglycerol O‐acyltransferase (DGAT) 1 and 2 are potentially important contributors to alcoholic steatosis. Our goal was to study the effects of dietary fat content on alcohol‐induced hepatic TG accumulation, and the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis.MethodsThese studies were carried out in wild‐type (WT) mice fed alcohol‐containing high‐fat or low‐fat formulations of Lieber‐DeCarli liquid diets, as well as follow‐up studies in Dgat1 −/− mice.ResultsA direct comparison of the low‐fat and high‐fat liquid diet in WT mice revealed surprisingly similar levels of alcoholic steatosis, although there were underlying differences in the pattern of hepatic lipid accumulation and expression of genes involved in hepatic lipid metabolism. Follow‐up studies in Dgat1 −/− mice revealed that these animals are protected from alcoholic steatosis when consumed as part of a high‐fat diet, but not a low‐fat diet.ConclusionsDietary macronutrient composition influences the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis, such that in the context of alcohol and a high‐fat diet, DGAT1 predominates.

Investigation of the effect of dietary fat content on obesity and metabolic syndrome in smokers

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Differential Effects of Dietary Fat Content and Protein Source on Bone Phenotype and Fatty Acid Oxidation in Female C57Bl/6 Mice.

BackgroundGlycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide released from κ-casein during cheesemaking that promotes satiety, reduces body fat, increases bone mass and infers prebiotic and anti-inflammatory effects. The impact of adiposity and gender on bone health is unclear.ObjectiveTo determine how feeding female mice diets providing 60% Fat Kcal (high-fat) or 13% Fat Kcal (control) with either GMP or casein as the protein source impacts: body composition, ex vivo fatty acid oxidation, bone (femoral) biomechanical performance, and the relationship between body composition and bone.MethodsWeanling female C57Bl/6 mice were fed high-fat (60% Fat Kcal) or control diets (13% Fat Kcal) with GMP or casein from 3 to 32 weeks of age with assessment of body weight and food intake. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Fatty acid oxidation was measured in liver, muscle, and fat tissues using 14C-palmitate. Plasma concentrations of hormones and cytokines were determined. Bone biomechanical performance was assessed by the 3-point bending test.ResultsFemale mice fed high-fat diets showed increased fatty acid oxidation capacity in both gastrocnemius muscle and brown adipose tissue compared to mice fed the control diets with a lower fat content. Despite increased fat mass in mice fed the high-fat diets, there was little evidence of glucose impairment or inflammation. Mice fed the high-fat diets had significantly greater total body bone mineral density (BMD), femoral BMD, and femoral cross-sectional area than mice fed the control diets. Femora of mice fed the high-fat diets had increased yield load and maximum load before fracture, consistent with greater bone strength, but reduced post-yield displacement or ductility, consistent with bone brittleness. Female mice fed a high-fat GMP diet displayed increased fat oxidation capacity in subcutaneous fat relative to mice fed the high-fat casein diet. Regardless of dietary fat content, GMP increased total body bone mineral content and femur length. The prebiotic properties of GMP may mediate the beneficial effects of GMP on bone.ConclusionsFemale mice adapt to high-fat feeding by increasing oxidative capacity in muscle tissue and to a lesser extent brown adipose tissue. High-fat feeding in female mice leads to development of a bone phenotype where femora show increased BMD and are stronger, yet more brittle. The increased brittleness of bone was associated with increased body fat content due to high-fat feeding. In summary, high-fat feeding in female mice increases mineralization of bone, but negatively impacts bone quality resulting in brittle bones.

Effects of dietary fat and saturated fat content on liver fat and markers of oxidative stress in overweight/obese men and women under weight-stable conditions.

Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change −2.13% (−3.74%, −0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.

Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue

Growing evidence shows that dietary factors can dramatically alter the gut microbiome in ways that contribute to metabolic disturbance and progression of obesity. In this regard, mesenteric adipose tissue has been implicated in mediating these processes through the elaboration of proinflammatory adipokines. In this study, we examined the relationship of these events by determining the effects of dietary fat content and source on gut microbiota, as well as the effects on adipokine profiles of mesenteric and peripheral adipocytes. Adult male C57Bl/6 mice were fed milk fat-based, lard-based (saturated fatty acid sources), or safflower oil (polyunsaturated fatty acid)-based high-fat diets for 4 weeks. Body mass and food consumption were measured. Stool 16S ribosomal RNA (rRNA) was isolated and analyzed via terminal restriction fragment length polymorphism as well as variable V3-4 sequence tags via next-generation sequencing. Mesenteric and gonadal adipose samples were analyzed for both lipogenic and inflammatory mediators via quantitative real-time polymerase chain reaction. High-fat feedings caused more weight gain with concomitant increases in caloric consumption relative to low-fat diets. In addition, each of the high-fat diets induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profiles of mesenteric and gonadal fat depots. Our findings support the notion that dietary fat composition can both reshape the gut microbiota and alter host adipose tissue inflammatory/lipogenic profiles. They also demonstrate the interdependency of dietary fat source, commensal gut microbiota, and inflammatory profile of mesenteric fat that can collectively affect the host metabolic state.

Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues

BackgroundDOR/TP53INP2 acts both at the chromosomal level as a nuclear co-factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as an organizing factor of the autophagosome. In a previous study, DOR was shown to be down-regulated in skeletal muscle of obese diabetic Zucker fa/fa rats.MethodsTo identify sites of differential DOR expression in metabolically active tissues, we measured differences in DOR expression in white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle (SM) and heart muscle (HM) by qPCR. To assess whether DOR expression is influenced in the short term by nutritional factors, NMRI mice were fed different fat rich diets (fat diet, FD: 18% or high fat diet, HFD: 80% fat) for one week and DOR expression was compared to NMRI mice fed a control diet (normal diet, ND: 3.3% fat). Additionally, DOR expression was measured in young (45 days old) and adult (100 days old) genetically obese (DU6/DU6i) mice and compared to control (DUKs/DUKsi) animals.ResultsANOVA results demonstrate a significant influence of diet, tissue type and sex on DOR expression in adipose and muscle tissues of FD and HFD mice. In SM, DOR expression was higher in HFD than in FD male mice. In WAT, DOR expression was increased compared to BAT in male FD and HFD mice. In contrast, expression levels in female mice were higher in BAT for both dietary conditions.DOR expression levels in all tissues of 100 days old genetically obese animals were mainly influenced by sex. In HM, DOR expression was higher in male than female animals.ConclusionsDOR expression varies under the influence of dietary fat content, tissue type and sex. We identified target tissues for further studies to analyze the specific function of DOR in obesity. DOR might be part of a defense mechanism against fat storage in high fat diets or obesity.

Oxidation of Dietary Stearic, Oleic, and Linoleic Acids in Growing Pigs Follows a Biphasic Pattern ,

We used the pig as a model to assess the effects of dietary fat content and composition on nutrient oxidation and energy partitioning in positive energy balance. Pigs weighing 25 kg were assigned to either: 1) a low fat–high starch diet, or 2) a high saturated-fat diet, or 3) a high unsaturated-fat diet. In the high-fat treatments, 20% starch was iso-energetically replaced by 10.8% lard or 10.2% soybean oil, respectively. For 7 d, pigs were fed twice daily at a rate of 1200 kJ digestible energy · kg-0.75· d-1. Oral bolus doses of [U-13C] glucose, [U-13C] a-linoleate, [U-13C] stearate, and [U-13C] oleate were administered on d 1, 2, 4, and 6, respectively, and13CO2production was measured. Protein and fat deposition were measured for 7 d. Fractional oxidation of fatty acids from the low-fat diet was lower than from the high-fat diets. Within diets, the saturated [U-13C] stearate was oxidized less than the unsaturated [U-13C] oleate and [U-13C] linoleate. For the high unsaturated-fat diet, oxidation of [U-13C] oleate was higher than that of [U-13C] linoleate. In general, recovery of13CO2from labeled fatty acids rose within 2 h after ingestion but peaked around the next meal. This peak was induced by an increased energy expenditure that was likely related to increased eating activity. In conclusion, oxidation of dietary fatty acids in growing pigs depends on the inclusion level and composition of dietary fat. Moreover, our data suggest that the most recently ingested fatty acids are preferred substrates for oxidation when the direct supply of dietary nutrients has decreased and ATP requirements increase.

The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent

A high-saturated-fat diet (HFD) induces obesity and insulin resistance (IR). IR has been linked to alterations and increased saturation in the phospholipid composition of skeletal muscles. We aimed to determine whether HFD feeding affects fatty acid (FA) membrane profile in a muscle fiber type-specific manner. We measured phospholipid FAs and expression of FA synthesis genes in oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles from rats fed either standard chow (standard laboratory diet, SLD) or a HFD. The HFD increased fat mass, plasma insulin, and leptin levels. Compared with EDL, SOL muscles preferentially accumulated C18 over C16 FAs and n-6 over n-3 polyunsaturated FAs (PUFAs) on either diet. With the HFD, SOL muscles contained more n-9 monounsaturated FAs (MUFAs) and n-6 PUFAs and less n-7 MUFAs and n-3 PUFAs than EDL muscles and had lower unsaturation index, a pattern known to be associated with IR. Stearoyl-CoA desaturase-1 expression was approximately 13-fold greater in EDL than in SOL muscles but did not change with the HFD in either muscle. The expression of Elongase-5 was higher, and that of Elongase-6 (Elovl6) was lower in EDL compared with SOL muscles with both diets. In EDL muscles, the expression of Elovl6 was lower in the HFD than in the SLD. The pattern of FA uptake, expression, and diet-induced changes in FA desaturating and elongating enzymes maintained higher FA unsaturation in EDL muscles. Accordingly, the fiber type composition of skeletal muscles and their distribution may be important in the development and progression of obesity and IR.

Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model

Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were fed either a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative reverse transcriptase polymerase chain reaction for lipid metabolism-related gene expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain, insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric intake. Quantitative reverse transcriptase polymerase chain reaction revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet compared with 10%-fat–fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low-fat diets deserve attention in the investigation of a potential treatment of patients with nonalcoholic fatty liver disease.

Pancreatic response in healthy dogs fed diets of various fat compositions

To indirectly assess the pancreatic response in healthy dogs that were fed diets of different fat compositions with or without supplemental pancreatic enzymes and medium-chain triglycerides (MCTs). 10 healthy adult dogs. Dogs were fed 4 diets once in random order at 1-week intervals; food was withheld from the dogs for > or = 12 hours prior to the feeding of each diet. Diets A and B contained 16% and 5% crude fat, respectively; diet C was composed of diet A with pancreatic enzymes; and diet D was composed of diet B with pancreatic enzymes and MCTs. Serum canine trypsin-like immunoreactivity (cTLI) and canine pancreatic lipase immunoreactivity (cPLI) concentrations were measured before (0 hours) and at 1 to 2 and 6 hours after feeding. Serum gastrin concentration was measured at 0 hours and at 5 to 10 minutes and 1 to 2 hours after feeding. A gastrin assay validation study was performed to confirm accuracy of test results in dogs. Data were analyzed by use of a repeated-measures general ANOVA. Serum cTLI, cPLI, or gastrin concentrations in the dogs did not differ among the different diets fed, among dogs, or over time. When multiple comparisons were analyzed, diet D caused the least amount of measurable pancreatic response, although this difference was not significant. Results did not indicate a significant effect of dietary fat content or addition of supplemental MCT oil or pancreatic enzymes in diets on serum cTLI, cPLI, or gastrin concentrations in healthy dogs.

Regional Heterogeneity of Functional Changes in Conduit Arteries After High‐fat Diet

To determine effects of dietary fat content on vascular responses in different conduit arteries in mice. Vascular responses to reactive oxygen species (ROS)/hydroxyl radical (.OH), acetylcholine (ACh), endothelin-1 (ET-1), and angiotensin II (Ang II) were determined in carotid and femoral arteries of C57BL/6J mice fed with diets varying in fat content (low fat (LF), 12.3%; high fat (HF), 41%; and very high fat (VHF), 58% (kcal from fat)) for 15 weeks, beginning at 4 weeks of age. In precontracted rings of carotid and femoral artery, ROS/.OH-induced a rapid, transient vasodilation. In the carotid, but not in femoral artery, ROS/.OH-induced dilation increased with increasing dietary fat intake (P < 0.05 vs. LF diet), while contractile responses to ROS/.OH remained unaffected. In femoral arteries, ROS/.OH-induced contractions were reversed into relaxations after both HF and VHF diet (P < 0.05 vs. LF diet). Both ET-1 and Ang II induced strong contractions in the femoral artery that were unaffected by dietary fat intake. In contrast, in the carotid artery Ang II-induced contraction was attenuated after HF and VHF diets (P < 0.005 vs. LF diet), whereas ET-1-induced vasoconstriction was significantly increased (P < 0.05 VHF vs. LF and HF). Treatment with VHF diet enhanced ACh-mediated endothelium-dependent relaxation only in the femoral artery (P < 0.05 vs. HF). These findings demonstrate that dietary fat content has regional and distinct effects on vascular function in different vascular beds. The data also suggest the possibility that in selected conduit arteries ROS-dependent vasodilator mechanisms become activated in response to increased dietary fat intake.

Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity

Angiotensin II (Ang II), endothelin-1 (ET-1) and reactive oxygen species (ROS) have been implicated in the development of pathologic changes associated with obesity including hypertension and atherosclerosis. The aim of this study was to investigate the effects of dietary fat content on vasoreactivity and receptor expression at the level of gene and protein expression. C57BL/6 mice were fed diets of normal (Control, 12.3% kcal from fat), high (HF, 41% kcal from fat) and very high (VHF, 58% kcal from fat) fat content for 15 weeks. Glucose tolerance tests were performed, and aortic rings were exposed to ET-1 (0.01-300 nM) and Ang II (100 nM) in the presence of L-nitro-arginine-methyl ester (L-NAME; 300 microM). Gene and protein expressions of angiotensin and endothelin receptors were examined by real-time PCR and immunoblotting, respectively. The effects of diet on responses to acetylcholine (ACh 0.1-300 microM), in the absence or presence of L-NAME, and to exogenous ROS/.OH were also investigated. Both high fat diets similarly impaired glucose tolerance (P<0.05). Increasing dietary fat augmented contractions to Ang II in a step-wise manner (P<0.05). Conversely, increasing dietary fat had no effect on contractions to ET-1. Exposure to ROS/.OH resulted in a rapid vasodilation that was markedly augmented in a step-wise manner with increasing dietary fat (P<0.05). Endothelium-dependent relaxation to ACh was unaffected whereas vasoconstriction to high concentrations of ACh was enhanced in VHF animals (P<0.05 vs. control). Gene expression of the AT(1B) receptor was increased in the aorta of VHF mice, and aortic ET(A) receptor protein expression was increased after both high fat diets. These findings demonstrate that changes in dietary fat intake modulate vascular reactivity in response to Ang II and ROS, as well as expression of vascular angiotensin and endothelin receptors. Dietary fat intake may thereby directly affect cardiovascular risk.

Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans

Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce. The objective of the study was to establish the effect of dietary fat content on the metabolism of primary bile salts. The effects of eucaloric extremely low-fat (0%), intermediate-fat (41%; control diet), and extremely high-fat (83%) diets on kinetic values of cholate and chenodeoxycholate metabolism were determined after 11 d by using stable isotope dilution in 6 healthy men. All diets contained identical amounts of cholesterol. The total primary bile salt pool size was not significantly affected by dietary fat content, although the chenodeoxycholate pool was significantly higher during the low-fat diet. Fractional turnover rates of both primary bile salts were 30-50% lower during the low- and high-fat diets than during the control diet. Total hepatic bile salt synthesis was approximately 30% lower during both the high- and low-fat diets, but synthesis rates of the 2 primary bile salts were differentially affected. The molar ratio of cholate to total bile salt synthesis increased from 0.50 +/- 0.05 ( +/- SD) to 0.59 +/- 0.05 and 0.66 +/- 0.04 with increasing fat intake, whereas the molar ratio of chenodeoxycholate to total bile salt synthesis decreased from 0.50 +/- 0.05 to 0.41 +/- 0.05 and 0.34 +/- 0.04. The relative concentration of deoxycholate in plasma increased during the low-fat period, which indicated increased absorption from the colon. Both low- and high-fat diets reduce the synthesis and turnover rates of primary bile salts in humans, although probably through different mechanisms, and consequently they affect the removal of cholesterol from the body.