Dietary fiber

Dietary fiber is plant-derived material that is resistant to digestion by human alimentary enzymes. Fiber may be divided into two broad chemical classes: 1) non-alpha-glucan polysaccharides (cellulose, hemicelluloses, and pectins) and 2) lignins. Dietary fiber behaves within the gastrointestinal tract as a polymer matrix with variable physicochemical properties including susceptibility to bacterial fermentation, water-holding capacity, cation-exchange, and adsorptive functions. These properties determine physiological actions of fiber and are dependent on the physical and chemical composition of the fiber. Fiber undergoes compositional changes as a consequence of bacterial enzymatic action in the colon. Dietary fiber is of clinical significance in certain disorders of colonic function and in glucose and lipid metabolism. Dietary fiber increases stool bulk by acting as a vehicle for fecal water and by increasing fecal bacterial volume. Use of fiber in the treatment of constipation and uncomplicated diverticular disease is well established. By increasing stool bulk, fiber also reduces the fecal concentration of bile acids and other substances. Certain types of fiber decrease the rate of glucose absorption and attenuate postprandial rises in blood glucose and insulin. Plasma cholesterol levels are reduced by mucilaginous forms of fiber. This effect appears to be mediated in part by an increase in fecal acidic sterol excretion.     

Numerical simulation of fibrous biomaterials with randomly distributed fiber network structure

This paper presents a computational framework to simulate the mechanical behavior of fibrous biomaterials with randomly distributed fiber networks. A random walk algorithm is implemented to generate the synthetic fiber network in 2D used in simulations. The embedded fiber approach is then adopted to model the fibers as embedded truss elements in the ground matrix, which is essentially equivalent to the affine fiber kinematics. The fiber–matrix interaction is partially considered in the sense that the two material components deform together, but no relative movement is considered. A variational approach is carried out to derive the element residual and stiffness matrices for finite element method (FEM), in which material and geometric nonlinearities are both included. Using a data structure proposed to record the network geometric information, the fiber network is directly incorporated into the FEM simulation without significantly increasing the computational cost. A mesh sensitivity analysis is conducted to show the influence of mesh size on various simulation results. The proposed method can be easily combined with Monte Carlo (MC) simulations to include the influence of the stochastic nature of the network and capture the material behavior in an average sense. The computational framework proposed in this work goes midway between homogenizing the fiber network into the surrounding matrix and accounting for the fully coupled fiber–matrix interaction at the segment length scale, and can be used to study the connection between the microscopic structure and the macro-mechanical behavior of fibrous biomaterials with a reasonable computational cost.     

Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet

Background: We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon‐like peptide‐1 (GLP‐1). Objective: Our objective was to combine, in one diet, high levels of fiber and protein to maximize GLP‐1 secretion, improve glucose tolerance, and reduce weight gain. Methods and Procedures: Lean (+/?) and obese (cp/cp) male James C Russell corpulent (JCR:LA‐cp) rats lacking a functional leptin receptor were fed one of four experimental diets (control, high protein (HP), high fiber (HF, prebiotic fiber inulin), or combination (CB)) for 3 weeks. An oral glucose tolerance test (OGTT) was performed to evaluate plasma GLP‐1, insulin and glucose. Plasma lipids and intestinal proglucagon mRNA expression were determined. Results: Energy intake was lower with the HF diet in lean and obese rats. Weight gain did not differ between diets. Higher colonic proglucagon mRNA in lean rats fed a CB diet was associated with higher GLP‐1 secretion during OGTT. The HP diet significantly reduced plasma glucose area under the curve (AUC) during OGTT in obese rats, which reflected both an increased GLP‐1 AUC and higher fasting insulin. Diets containing inulin resulted in the lowest plasma triglyceride and total cholesterol levels. Discussion: Overall, combining HP with HF in the diet increased GLP‐1 secretion in response to oral glucose, but did not improve glucose tolerance or lipid profiles more than the HF diet alone did. We also suggest that glycemic and insulinemic response to prebiotics differ among rat models and future research work should examine their role in improving glucose tolerance in diet‐induced vs. genetic obesity with overt hyperleptinemia.     

Coupling of concanavalin A to cellulose hollow fibers for use in glucose affinity sensor

This article describes a method for the chemical immobilization of concanavalin A (Con A) on the inside wall of a single hollow cellulose fiber for use in glucose affinity sensor. Periodate oxidation of cellulose fiber followed by a spacer for Con A attachment was deemed to be the most optimal procedure for achieving the highest sensitivity of the sensor without compromising its physical integrity. The effects of variables like the duration of periodate oxidation and its concentration and pH of the spacer coupling step and its duration have been examined. The mechanical strength of the hollow fiber as well as its permeability to the analyte (glucose) have been evaluated prior to and after Con A coupling process.It has been demonstrated that Con A bound hollow fiber prepared according to the procedure outlined here can be successfully used to construct glucose affinity sensor for operation in the physiological range of glucose concentrations.     

Effects of elevated glucose levels on interactions of cardiac fibroblasts with the extracellular matrix

Exposure of fibroblasts to high glucose levels promotes a fibrotic response characterized by increased expression of extracellular matrix components including interstitial collagens. Little is known about the effects of glucose levels on other aspects of fibroblast function. Fibroblasts in the myocardium are surrounded by an extensive extracellular matrix composed predominantly of type I collagen. Interactions between fibroblasts and the myocardial extracellular matrix are thought to affect heart function by altering ventricular diastolic properties. The purpose of the present study was to determine the effects of elevated glucose levels on the interactions between heart fibroblasts and the collagenous extracellular matrix. Studies were performed to determine the effects of relative glucose levels on the ability of fibroblasts to migrate on and contract a three-dimensional collagenous substratum. These experiments illustrated that exposure of cardiac fibroblasts to high glucose levels (25 mM) resulted in decreased migratory activity of fibroblasts on a collagen matrix and decreased fibroblast proliferation. In addition, high glucose stimulated collagen and collagen-binding integrin expression and contraction of three-dimensional collagen gels by cardiac fibroblasts. These studies illustrate that altered glucose levels induce important changes in the interactions of cardiac fibroblasts with the collagenous extracellular matrix. Xiaoyi Zhang and James A. Stewart, Jr. are co-first authors.     

Multi-day pre-clinical demonstration of glucose/galactose binding protein-based fiber optic sensor

We report here the first pre-clinical demonstration of continuous glucose tracking by fluorophore-labeled and genetically engineered glucose/galactose binding protein (GGBP). Acrylodan-labeled GGBP was immobilized in a hydrogel matrix at the tip of a small diameter optical fiber contained in a stainless steel needle. The fiber optic biosensors were inserted subcutaneously into Yucatan and Yorkshire swine, and the sensor response to changing glucose levels was monitored at intervals over a 7-day period. Sensor mean percent error on day 7 was 16.4±5.0% using a single daily reference blood glucose value to calibrate the sensor. The GGBP sensor's susceptibility to common interferents was tested in a well-plate system using human sera. No significant interference was observed from the tested interferents except for tetracycline at the drug's maximum plasma concentration. The robust performance of the GGBP-based fiber optic sensor in swine models and resistance to interferents indicates the potential of this technology for continuous glucose monitoring in humans.     

Evaluation of Serum Selenium Levels in Turkish Women with Gestational Diabetes Mellitus, Glucose Intolerants, and Normal Controls

The aim of the study was to investigate the association between serum selenium levels in patients with gestational diabetes mellitus (GDM) and glucose intolerants and compare them with those of glucose-tolerant pregnant women. This cross-sectional study was prospectively performed in a total of 178 pregnant women undergoing a 50-g oral glucose tolerance test between 24 and 28 weeks of gestation who were grouped according to their status of glucose tolerance as with gestational diabetes (group A, abnormal 1- and 3-h glucose tolerance test; n = 30), glucose intolerant (group B, abnormal 1-h but normal 3-h glucose tolerance test; n = 47), or normal controls (group C, normal 1-h glucose test; n = 101). Serum selenium levels were measured with a graphite furnace atomic absorption spectrophotometer using a matrix modifier. Median maternal age and gestational age at the time of diagnosis in group A (gestational age = 24.8 [24-27]), group B (gestational age = 24.7 [24-27]), and group C (gestational age = 25 [24-28]) did not differ. Patients with gestational diabetes mellitus and those with glucose intolerants had lower selenium level than that of the normal pregnant women (P < 0.001). There was a significant inverse correlation between selenium and blood glucose level, and also selenium supplementation might prove beneficial on patients with GDM and prevent or retard them from secondary complications of diabetes.     

Functional and Muscular Adaptations in an Experimental Model for Isometric Strength Training in Mice

Exercise training induces muscular adaptations that are highly specific to the type of exercise. For a systematic study of the differentiated exercise adaptations on a molecular level mouse models have been used successfully. The aim of the current study was to develop a suitable mouse model of isometric strength exercise training characterized by specific adaptations known from strength training. C57BL/6 mice performed an isometric strength training (ST) for 10 weeks 5 days/week. Additionally, either a sedentary control group (CT) or a regular endurance training group (ET) groups were used as controls. Performance capacity was determined by maximum holding time (MHT) and treadmill spirometry, respectively. Furthermore, muscle fiber types and diameter, muscular concentration of phosphofructokinase 1 (PFK), succinate dehydrogenase (SDHa), and glucose transporter type 4 (GLUT4) were determined. In a further approach, the effect of ST on glucose intolerance was tested in diabetic mice. In mice of the ST group we observed an increase of MHT in isometric strength tests, a type II fiber hypertrophy, and an increased GLUT4 protein content in the membrane fraction. In contrast, in mice of the ET group an increase of VO_2max, a shift to oxidative muscle fiber type and an increase of oxidative enzyme content was measured. Furthermore strength training was effective in reducing glucose intolerance in mice fed a high fat diet. An effective murine strength training model was developed and evaluated, which revealed marked differences in adaptations known from endurance training. This approach seems also suitable to test for therapeutical effects of strength training.     

Reference values for 75 g oral glucose tolerance test in pregnancy

A 75 g oral glucose tolerance test was performed in 212 pregnant women with no predisposing factors suggesting glucose intolerance to establish the normal pattern of glucose metabolism in pregnancy. Reference values for the test were established for the middle of pregnancy (14-20 weeks, n=43) and late pregnancy (28-37 weeks, n=168). One woman was excluded because she had diabetes that required treatment with insulin. There were statistically significant differences between the two groups for samples taken both one and two hours after the glucose load. Reference ranges for the interpretation of the glucose tolerance test in pregnancy should therefore take account of the period of gestation.Arbitrary upper limits of normal (represented by the 97·5 centile) two hours after a 75 g oral glucose load are proposed at 7·5 and 9·6 mmol/l for the second and third trimesters, respectively.     

Abnormal Skeletal Muscle Regeneration plus Mild Alterations in Mature Fiber Type Specification in Fktn-Deficient Dystroglycanopathy Muscular Dystrophy Mice

Glycosylated α-dystroglycan provides an essential link between extracellular matrix proteins, like laminin, and the cellular cytoskeleton via the dystrophin-glycoprotein complex. In secondary dystroglycanopathy muscular dystrophy, glycosylation abnormalities disrupt a complex O-mannose glycan necessary for muscle structural integrity and signaling. Fktn-deficient dystroglycanopathy mice develop moderate to severe muscular dystrophy with skeletal muscle developmental and/or regeneration defects. To gain insight into the role of glycosylated α-dystroglycan in these processes, we performed muscle fiber typing in young (2, 4 and 8 week old) and regenerated muscle. In mice with Fktn disruption during skeletal muscle specification (Myf5/Fktn KO), newly regenerated fibers (embryonic myosin heavy chain positive) peaked at 4 weeks old, while total regenerated fibers (centrally nucleated) were highest at 8 weeks old in tibialis anterior (TA) and iliopsoas, indicating peak degeneration/regeneration activity around 4 weeks of age. In contrast, mature fiber type specification at 2, 4 and 8 weeks old was relatively unchanged. Fourteen days after necrotic toxin-induced injury, there was a divergence in muscle fiber types between Myf5/Fktn KO (skeletal-muscle specific) and whole animal knockout induced with tamoxifen post-development (Tam/Fktn KO) despite equivalent time after gene deletion. Notably, Tam/Fktn KO retained higher levels of embryonic myosin heavy chain expression after injury, suggesting a delay or abnormality in differentiation programs. In mature fiber type specification post-injury, there were significant interactions between genotype and toxin parameters for type 1, 2a, and 2x fibers, and a difference between Myf5/Fktn and Tam/Fktn study groups in type 2b fibers. These data suggest that functionally glycosylated α-dystroglycan has a unique role in muscle regeneration and may influence fiber type specification post-injury.     

Enhanced Lipid Oxidation and Maintenance of Muscle Insulin Sensitivity Despite Glucose Intolerance in a Diet-Induced Obesity Mouse Model

Background

Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity.

Methodology

C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes.

Principal Findings/Conclusions

A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle’s insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD.     

In‐situ monitoring of Saccharomyces cerevisiae ITV01 bioethanol process using near‐infrared spectroscopy NIRS and chemometrics

The application feasibility of in‐situ or in‐line monitoring of S. cerevisiae ITV01 alcoholic fermentation process, employing Near‐Infrared Spectroscopy (NIRS) and Chemometrics, was investigated. During the process in a bioreactor, in the complex analytical matrix, biomass, glucose, ethanol and glycerol determinations were performed by a transflection fiber optic probe immersed in the culture broth and connected to a Near‐Infrared (NIR) process analyzer. The NIR spectra recorded between 800 and 2,200 nm were pretreated using Savitzky‐Golay smoothing and second derivative in order to perform a partial least squares regression (PLSR) and generate the calibration models. These calibration models were tested by external validation and then used to predict concentrations in batch alcoholic fermentations. The standard errors of calibration (SEC) for biomass, ethanol, glucose and glycerol were 0.212, 0.287, 0.532, and 0.296 g/L and standard errors of prediction (SEP) were 0.323, 0.369, 0.794, and 0.507 g/L, respectively. Calibration and validation criteria were defined and evaluated in order to generate robust and reliable models for an alcoholic fermentation process matrix. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:510–517, 2016     

Pore and matrix distribution in the fiber wall revealed by atomic force microscopy and image analysis

A method for the ultrastructural investigation of fiber cross-sections based on atomic force microscopy in combination with image analysis is presented. A uniform distribution of pores across the matrix material within the fiber wall was revealed by impregnation of pulp fibers with poly(ethylene glycol). The effects of chemical and mechanical processing on the pore and matrix structure and on the arrangement of the cellulose fibril aggregates were investigated. During chemical processing, changes in the fiber ultrastructure occur: a broadening of the pore and matrix lamella widths in combination with a reduction in their number and an enlargement of the cellulose fibril aggregates. It was found that pores formed during pulping are evenly distributed across the fiber wall in the transverse direction. In contrast, refining increases the pore and matrix lamella width in the fiber wall closest to the middle lamella an effect which gradually decrease in size toward the lumen side.     

链脲佐菌素诱导C57小鼠1型糖尿病模型的研究

目的:通过小剂量多次腹腔注射链脲佐菌素(STZ)诱导建立与人类1型糖尿病相似的C57小鼠糖尿病模型,研究建模剂量和成模率。方法:将32只C57小鼠随机分为正常对照组(A)和实验组(B)。实验组(B)可分为低、中、高剂量组(50 mg/kg、70mg/kg、90 mg/kg)(n=8)。两组都喂普通饲料1周后,B组连续5天腹腔注射不同剂量STZ,测定注射前、注射后1周、2周、3周、4周、5周的空腹血糖和体重,观察小鼠饮食、饮水和排尿情况。STZ注射第3周进行口服糖耐量实验(OGTT)。结果:给药前A、B组体重和血糖无显著差异,给药1周后,B组饮水量和进食量明显增加,体重减轻。C57小鼠用药2周后,中剂量组达到建模标准,成模率75%。各剂量组均出现了糖耐量异常。结论:诱导建立C57小鼠1型糖尿病模型方法是连续5日腹腔注注射STZ,适宜剂量为70 mg/kg。     

Proteoglycans of alveolar bone of diabetic and non-diabetic mice: a histochemical study

The effect of diabetes mellitus on the interdental alveolar bone has been long debated. The present study reported the distribution of glycosaminoglycans (GAG) in normal and diabetic alveolar bone using histochemical techniques. Animals were rendered diabetic and killed at 2, 4, 6 and 9 weeks after injections. Tissues were stained with Alcian blue 8GX dye (pH 2.5) to demonstrate GAG and the intensity of the staining reactions compared with age-matched controls. During the experiment, weights of control animals did not change significantly; weights of diabetic animals were significantly less than initial weights from 0-6 weeks (p less than 0.001), but became nearly equal by 9 weeks. Staining intensity of diabetic bone demonstrated initial decrease (0-4 weeks) followed by a marked increase (4-9 weeks) suggesting an early decline in bone GAG levels followed by increased bone GAG levels as compared to age-matched control and initial levels. Bone GAG levels were significantly different between diabetics and age-matched controls at 2 (p less than 0.005) 4 (p less than 0.001), 6 (p less than 0.001) and 9 (p less than 0.001) weeks after streptozotocin injections. Digestion with chondroitinase AC, ABC and streptomyces hyaluronidase suggested significant differences between control and diabetic bone matrix in the levels of chondroitin 4 and 6 sulfates (p less than 0.05) and hyaluronic acid (p less than 0.001) but not dermatan sulfate. In control and diabetic bone, chondroitin sulfates were located within the bone matrix, dermatan sulfate within bone matrix and Sharpey fiber bundles.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of a cell-free perfusate in the perfused rat hindquarter: methodological concerns

The viability of using a cell-free perfusate in a rat hindlimb preparation to assess skeletal muscle glycogenesis was investigated. A perfusate containing 10 mM glucose and 10 microCi (1 Ci = 37 GBq) of D-[5-3H]glucose was recycled for a 60-min period. In agreement with other studies using more complex media, oxygen uptake of the preparation indicated adequate tissue oxygenation (8 mumol.min-1.g-1). Skeletal muscle fiber type heterogeneity in basal glycogen synthesis from glucose was shown (slow oxidative greater than fast oxidative glycolytic greater than fast glycolytic fibres). Insulin (4.2 mU/mL) markedly stimulated glycogenesis from D-[5-3H]glucose in the soleus (slow oxidative fiber), red gastrocnemius (fast oxidative glycolytic fiber), and white gastrocnemius muscles (p less than 0.05). A recent report indicates that tissue edema in this preparation did not affect insulin responsiveness of the tissue. In contrast, our observations indicate that glucos uptake was enhanced by insulin when edema was absent (p less than 0.05), but not when edema was present (p less than 0.05). In addition, the presence of tissue edema negated insulin-mediated glycogenesis in slow oxidative and fast oxidative glycolytic muscle (p less than 0.05 compared with control) but not in fast glycolytic muscle (p less than 0.05). These data warrant caution when using a cell-free media in the perfused rat hindquarter; however, in the absence of edema, normal responses of glucose metabolism are observed.     

SHR的胰岛素抗性及骨胳肌的形态学特征

本文研究了自发性高血压大鼠及其对照品系－正常血压大鼠的胰岛素抗性和肌肉组织的形态学差异。结果表明：ＳＨＲ的基础胰岛素水平,糖耐量实验时胰岛素曲线下的面积均高于ＷＫＹ。而基础血糖水平,ＧＴＴ时血糖曲线下的面积两者相似。组织形态学研究表明：ＳＨＲ内胳肌中对胰岛素长一智Ⅰ型纤维比例低于ＷＫＹ。本研究发现：基础胰岛素水平或ＧＴＴ时胰岛素曲线下的面积与血压之间有正相关关系,而基础胰岛素水平与骨胳肌中Ｉ型纤维     

Theoretical analysis of the effect of convective flow on solute transport and insulin release in a hollow fiber bioartificial pancreas

The bioartificial pancreas, in which transplanted pancreatic tissue or isolated cells are cultured on a hollow fiber membrane, is an attractive approach to restore physiologic insulin delivery in the treatment of diabetes. Insulin response in prototype devices has been unacceptable due to the large mass transport limitations associated with the membrane and the surrounding shell region. Although available theoretical analyses provide some insight into the combined effects of transport and reaction in the bioartificial pancreas, they cannot quantitatively account for the effects of convective recirculation flow, complex intrinsic insulin secretory kinetics, and non-uniform distribution of pancreatic cells. We have developed a detailed model for glucose and insulin transport and insulin secretion in the hollow fiber bioartificial pancreas based on the solution of the mass and momentum conservation equations describing flow and transport in the lumen, matrix, and shell. Model predictions are in good agreement with literature data obtained in a hollow fiber device with minimal radial convective flow. Although no quantitative data are available for a device with significant radial convection, model simulations demonstrate that convective recirculation flow can dramatically improve insulin response, allowing the device to accurately capture the bi-phasic insulin secretion characteristic of the normal physiologic response. Results provide fundamental insights into the coupling between kinetics and transport in the hollow fiber system and a rational basis for the design of clinical devices.     

Molecular analysis of fibulin-5 function during de novo synthesis of elastic fibers

Elastic fibers contribute to the structural support of tissues and to the regulation of cellular behavior. Mice deficient for the fibulin-5 gene (fbln5(-/-)) were used to further elucidate the molecular mechanism of elastic fiber assembly. Major elastic fiber components were present in the skin of fbln5(-/-) mice despite a dramatic reduction of mature elastic fibers. We found that fibulin-5 preferentially bound the monomeric form of elastin through N-terminal and C-terminal elastin-binding regions and to a preexisting matrix scaffold through calcium-binding epidermal growth factor (EGF)-like (CB-EGF) domains. We further showed that adenovirus-mediated gene transfer of fbln5 was sufficient to regenerate elastic fibers and increase elastic fiber-cell connections in vivo. A mutant fibulin-5 lacking the first 28 amino acids of the first CB-EGF domain, however, was unable to rescue elastic fiber defects. Fibulin-5 thus serves as an adaptor molecule between monomeric elastin and the matrix scaffold to aid in elastic fiber assembly. These results also support the potential use of fibulin-5 as a therapeutic agent for the treatment of elastinopathies.     

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.