Human Body Fat Research Articles

Visceral Fat Increases Cardiometabolic Risk Factors Among Type 2 Diabetes Patients

The aim of this study is to discuss the increase in risk for obesity-related disorders. It is believed that such complications arise due to store of visceral fat. The visceral fat is considered as an independent predictor of all-cause of mortality among type 2 diabetes (T2D) patients. Higher visceral fat is associated with an adverse lipid and glucose profile. Accumulation of visceral fat is located inside the abdominal cavity and surrounds internal organs, such as in the liver, stomach, kidneys, pancreas, intestines, and heart. Store of visceral adipose tissue (VAT) is characterized as pro-inflammatory, metabolically active, and susceptible to lipolysis. This study tries to present briefly the harmful activities of visceral fat in human body.

A polyphenol fraction from Rosa multiflora var. platyphylala reduces body fat in overweight humans through appetite suppression - a randomized, double-blind, placebo-controlled trial.

Rosa species are rich sources of polyphenols with physiological functions. In this study a polyphenol-rich Rosa multiflora (var. platyphylala) petal extract (RoseFit™) was investigated for weight loss in humans. In a randomized, placebo-controlled, parallel-group, double-blind clinical trial seventy overweight male and female subjects (20-50 years) with body mass index (BMI) 25-30kg/m2 were randomly allocated to the active treatment group (RoseFit) and placebo group in a 1:1 ratio. The subjects received 300mg capsules twice daily for 12 weeks. The primary efficacy outcome measures included body weight, BMI, and body composition, as determined using Dual-energy X-ray absorptiometry (DEXA). Secondary measures consisted of serum lipid profile and appetite marker (leptin and ghrelin) analyses. Safety analyses included biochemical and hematological assessments. At the end of the study, a marked reduction in body weight (-1.20 ± 2.62kg, p < 0.05) and BMI from baseline was observed in the RoseFit group. In addition, the body fat % (RoseFit = -1.69 ± 2.59%, placebo = 0.96 ± 3.21%; p < 0.001) and fat mass (RoseFit = -1.75 ± 1.80kg, placebo = 1.61 ± 3.82kg; p < 0.001) were significantly abated in RoseFit group. Importantly, the lean mass was maintained during the intervention. RoseFit ingestion significantly increased the serum leptin levels compared to the placebo (4.85%; p < 0.05). Further, RoseFit group showed reduction in the hunger hormone ghrelin level (2.27%; p < 0.001) from baseline to the end of study, compared to the placebo. The subjective evaluation of appetite using visual analog scale (VAS) questionnaires further confirmed the appetite-suppression effects of RoseFit. The lipid profile significantly improved in RoseFit-treated subjects. No serious adverse events were observed during the study, indicating the tolerability of RoseFit. Supplementation with RoseFit significantly impacts body weight management and can thus be a potential nutraceutical ingredient for sustainable weight loss. CTRI/2019/10/021584 dated 09/10/2019.

Sex-based approach to estimate human body fat percentage from 2D camera images with deep learning and machine learning

Obesity is one of the most concerning nutritional issues since it is a significant risk factor for chronic diseases, including cardiovascular disease and diabetes. Many dietary disorders require an anthropometry assessment and body fat percentage (BFP) information. Dual-energy X-ray absorptiometry (DXA) is the most precise and automated method for determining BFP; nevertheless, it is costly and difficult to locate in clinics. This paper proposes the utilization of digital image processing and machine learning techniques to estimate BFP, considering four 2D camera images and additional factors such as age, weight, height, and sex. Our proposal specifically adopts a sex-specific approach. Our experiments included pre-processing steps and several regressors. Moreover, we built a dataset composed of 912 samples, including male and female individuals. The sex-based approach to estimating the BFP achieved satisfactory results for both males and females. Thus, it can assist monitor patients as a mobile application, especially in areas where experts and technology, such as equipment, are scarce.

A Study on Body Fat Percentage for Physical Fitness and Prevention of Obesity: A Two Compartment Model

The minimal amount of body fat is necessary for normal physiological functions that manages body temperature, creates energy to perform all the physical activities, and protects the organs of human body. Storage body fat consists of fat accumulation in adipose tissue. Total body fat in human body is the sum of essential fat and storage fat. At present body fat percentage is considered as one of the most accurate obesity evaluation tools. To determine body fat accurately the clinicians should use the most appropriate, accurate, and accessible strategies available in the scientific research area. Accurate measurement of body fat and lean body is essential for the nutrition assessment, and an individual’s overall health and well-being. In this study some measurement processes are discussed to determine body fat percentage (BFP) properly of a person by the analysis of two compartment model: fat mass and fat free mass.

Timing of Medium-Chain Triglyceride Consumption Modulates Effects in Mice with Obesity Induced by a High-Fat High-Sucrose Diet

The prevalence of obesity is increasing worldwide, and obesity can cause type 2 diabetes, atherosclerosis, hypertension, cardiovascular disease, and cancer. Intake of medium-chain triglycerides (MCTs) containing medium-chain fatty acids reduces body fat and insulin resistance in rodents and humans. This study aimed to determine how the timing of MCT consumption affects obesity and metabolic dysfunction induced in mice by a high-fat high-sucrose diet (HFHSD). Mice received an HFHSD with or without MCT (M-HFHSD) during either the active or rest phase for 9 weeks. Significant reduction in body weight, white adipose tissue (WAT) weight, and adipocyte size in epididymal WAT (eWAT) and improved insulin sensitivity in mice fed with M-HFHSD during the active but not the rest phase were observed. The consumption of M-HFHSD during both active and rest phases increased glucose tolerance. Phosphorylated Akt was more abundant in the gastrocnemius muscles and eWAT of M-HFHSD-fed mice than in those fed HFHSD during the active phase. The mRNA and protein expression of lipogenic genes increased in the eWAT of mice fed M-HFHSD compared with those fed HFHSD. Feeding with M-HFHSD during the active phase significantly increased the abundance of phosphorylated Ser563 and 660 of hormone-sensitive lipase and its upstream protein kinase A in eWAT. These results indicated that the timing of consumption modulates the effects of MCT on eWAT hypertrophy and glucose and lipid metabolism in mice.

Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy.

LMNA mutation is associated with type-2 familial partial lipodystrophy (FPLD2). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism. In human fibroblasts and preadipocytes, a trend for ATP production, mainly supported by mitochondrial oxidative metabolism, is detected. Moreover, primary cell lines with FPLD2 mutation decrease the mitochondrial ATP production if compared with the control, even if no differences are observed in the oxygen consumption rate of bioenergetic parameters (i.e., basal and maximal respiration, spare respiratory capacity, and ATP turnover). Conversely, glycolysis is only inhibited in FPLD2 fibroblast cell lines. We notice that the amount of ATP produced in the fibroblasts is higher than in the preadipocytes, and likewise in the control, with respect to FPLD2, due to a more active oxidative phosphorylation (OXPHOS) and glycolysis. Moreover, the proton leak parameter, which characterizes the transformation of white adipose tissue to brown/beige adipose tissue, is unaffected by FPLD2 mutation. The metabolic profile of fibroblasts and preadipocytes is confirmed by the ability of these cell lines to increase the metabolic potential of both OXPHOS and glycolysis under energy required independently by the FPLD2 mutation.

HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution.

Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.

Repeatability and Image Quality of IDEAL-IQ in Human Lumbar Vertebrae for Fat and Iron Quantification across Acquisition Parameters.

Echo asymmetry and least square estimation-IQ (IDEAL-IQ) were used to quantify fat and iron to verify the effects of collection parameters on repeatability and image quality of water and fat in human vertebral body. Six IDEAL-IQ sequences were used to scan 48 healthy adult women. Reproducibility of fat and iron quantification and image quality were assessed for six IDEAL-IQ sequences. The results showed that the correlation index (0.987, 0.721) of FF and R2∗ between scans of sequence 2 was higher than that of other sequences, and the consistency of fat quantification was better than that of iron (0.860 vs. 0.579) (P < 0.001). Sequence 2 had the highest image quality score (4.9) and the lowest CV score (9.2%). In the FF figure, SNR (18.8) and CNR (17.8 ± 6.4) were the highest, while CV was the lowest (36.7%, 36.1%). In the R2∗ figure, sequence 3 had the highest SNR (21.8) and CNR (20.5), but its CV (51.8% and 56.1%) was significantly higher than that of sequence 2. The occurrence of fat-water exchange (FWS) was lowest in sequence 2 and sequence 4 (0, N = 96). In conclusion, the fat quantification of IDEAL-IQ was robust to the changes of collection parameters, and section thickness (ST) had a certain effect on maintaining good repeatability of R2∗ quantification. The higher the ST was, the better the image quality of FF and R2∗ was maintained and stable and the less the occurrence of FWS.

Effect of walking exercise on the human body

Recent studies have demonstrated that brisk walking help to reduce anxiety and tension and assist in weight loss. Regular walking helps improve cholesterol profile, help control hypertension, and slow the process of osteoporosis. The purpose of this paper is to summarise the benefits of walking on physical and mental health to encourage people to participate in walking as a regular and sustainable exercise, and to determine of the limitation of regular walking. The researcher used the descriptive approach for achieve the research objectives. Research finding indicated that walking can relieve the human body fat, improve their heart health and decrease the possible risk of heart attack and stroke. Additionally walking improve their ability in lowering high blood pressure, reduce risk of diabetes, and Decrease stress and prevent depression.

Data Transmission Enhancement Using Optimal Coding Technique Over In Vivo Channel for Interbody Communication.

Wireless in vivo actuators and sensors are examples of sophisticated technologies. Another breakthrough is the use of in vivo wireless medical devices, which provide scalable and cost-effective solutions for wearable device integration. In vivo wireless body area networks devices reduce surgery invasiveness and provide continuous health monitoring. Also, patient data may be collected over a long period of time. Given the large fading in in vivo channels due to the signal path going through flesh, bones, skins, and blood, channel coding is considered a solution for increasing the efficiency and overcoming inter-symbol interference in wireless communications. Simulations are performed by using 50 MHz bandwidth at Ultra-Wideband frequencies (3.10-10.60 GHz). Optimal channel coding (Turbo codes, Convolutional codes, with the help of polar codes) improves data transmission performance over the in vivo channel in this research. Moreover, the results reveal that turbo codes outperform polar and convolutional codes in terms of bit error rate. Other approaches perform similarly when the information block length is increased. The simulation in this work indicates that the in vivo channel shows less performance than the Rayleigh channel due to the dense structure of the human body (flesh, skins, blood, bones, muscles, and fat).

Body fat compartment determination by encoder\u2013decoder convolutional neural network: application to amyotrophic lateral sclerosis

The objective of this study was to automate the discrimination and quantification of human abdominal body fat compartments into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from T1-weighted MRI using encoder-decoder convolutional neural networks (CNN) and to apply the algorithm to a diseased patient sample, i.e., patients with amyotrophic lateral sclerosis (ALS). One-hundred-and-fifty-five participants (74 patients with ALS and 81 healthy controls) were split in training (50%), validation (6%), and test (44%) data. SAT and VAT volumes were determined by a novel automated CNN-based algorithm of U-Net like architecture in comparison with an established protocol with semi-automatic assessment as the reference. The dice coefficients between the CNN predicted masks and the reference segmentation were 0.87 ± 0.04 for SAT and 0.64 ± 0.17 for VAT in the control group and 0.87 ± 0.08 for SAT and 0.68 ± 0.15 for VAT in the ALS group. The significantly increased VAT/SAT ratio in the ALS group in comparison to controls confirmed the previous results. In summary, the CNN approach using CNN of U-Net architecture for automated segmentation of abdominal adipose tissue substantially facilitates data processing and offers the opportunity to automatically discriminate abdominal SAT and VAT compartments. Within the research field of neurodegenerative disorders with body composition alterations like ALS, the unbiased analysis of body fat components might pave the way for these parameters as a potential biological marker or a secondary read-out for clinical trials.

THE INDIRECT INFLUENCE OF BASKETBALL ON CARDIAC AND CEREBRAL VASCULARIZATION

ABSTRACT Introduction: Some experimental research has proved that long-term basketball exercises can effectively improve physical fitness, promote growth and improve motor functions. However, studies exploring the specific effects of this sport on cardiac and cerebral vascularization are still scarce. Objective: We aimed to study, through experimental analysis, if the activities derived from basketball sport can have some influence on cardiac and cerebral vascularization. Methods: Twelve students with no family history of genetic diseases and in good health, who regularly practice amateur basketball, were followed for 8 weeks. Weight, height, body mass index, body fat rate, maximum oxygen consumption, hemoglobin, and indicators of lipid metabolism were analyzed. Results: After long-term basketball exercises, the body fat rate of these college students decreased significantly, and total serum cholesterol and low-density lipoprotein also show significant differences compared with the control group. Conclusion: Through the processing and analysis of the experimental data, it can be concluded that basketball can effectively reduce the human body fat rate, maintain a healthy body shape, and indirectly reduce the risk of cardiovascular and cerebrovascular diseases. Level of evidence II; Therapeutic studies - investigation of treatment results.

Chronic circadian disruption on a high-fat diet impairs glucose tolerance

BackgroundNearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods. MethodsWe investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to induce circadian misalignment between behaviors including rest/activity and fasting/eating with the output of the near-24-h central circadian pacemaker, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25–27% in humans) and high-fat diet (HFD, 45% in mouse and 45–50% in humans). We also used young vs. older mice to determine whether they would respond differently to RCD. ResultsWhen combined with a HFD, we found that RCD caused significant weight gain in mice and increased body fat in humans, and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice. ConclusionThese results in both humans and a model organism indicate that circadian disruption has an adverse effect on metabolism among individuals eating a high-fat Western-style diet, even in the absence of significant sleep loss, and suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.

Modern Classification of the Properties of Papillary Patterns of Human Hands and Feet for the Solution of Identification and Non-Identification Problems in Forensic Expert Activities

The relevance and novelty of the topic of the article is connected with the fact that for the first time the improved classification of the properties of human papillary patterns and their displays and the dynamic trend of expanding the legal base of fingerprint registration in the world are considered. The goal is to systematize the properties of human papillary patterns and their representations. General scientific and special methods were used. The analysis of the literature and the author's practice allow us to identify and consider the following properties of papillary patterns and their mappings, which were divided into three groups for cognitive purposes: their own properties, the properties of mappings, and the properties of the fat-rich substance of the human papillary pattern and its trace. For the first time, the properties of the poly-fat substance of the human papillary pattern and its trace are presented, which is important in view of the trend in the development of complex fingerprint examination. For the first time, the first and second groups are conditionally divided into four subgroups: for solving identification, diagnostic, classification and situational problems. For the first time, the third group is further conditionally divided into four subgroups: according to the interaction of the human body fat with the carrier object; according to the isolation of the human body fat trace; according to the dynamics of the preservation and contrast of the display of the fat-free substance of the human papillary pattern. On the other hand, the properties of papillary patterns themselves are divided into basic properties and properties for solving identification and non-identification problems, respectively. The author's definition of the following concepts is presented: "basic properties of human papillary patterns" and "properties of human papillary patterns", "basic properties of human papillary patterns mappings" and "properties of human papillary patterns mappings", "basic properties of human papillary matter" and "properties of human papillary matter", "basic properties of human papillary matter" and" properties of human papillary matter". This provides an opportunity for specialists and teachers to improve their cognitive and practical activities, and for those responsible and competent for the organization of examinations to consider creating a center for comprehensive fingerprint examination.

NLRP3 Inflammasome in Metabolic-Associated Kidney Diseases: An Update.

Metabolic syndrome (MS) is a group of complex metabolic disorders syndrome, which refers to the pathological state of metabolism disorder of protein, fat, carbohydrate and other substances in human body. The kidney is an important organ of metabolism, and various metabolic disorders can lead to the abnormalities in the structure and function of the kidney. The recognition of pathogenesis and treatment measures of renal damage in MS is a very important part for the renal function preserve. Inflammatory response caused by various metabolic factors is a protective mechanism of the body, but persistent inflammation will become a harmful factor and aggravate kidney damage. Inflammasomes are sensors of the innate immune system that play crucial roles in initiating inflammation in response to acute infections and chronic diseases. They are multiprotein complex composed of cytoplasmic sensors (mainly NLR family members), apoptosis-associated speck-like protein (ASC or PYCARD) and pro-caspase-1. After receiving exogenous and endogenous stimuli, the sensors begin to assemble inflammasome and then promote the release of inflammatory cytokines IL-1β and IL-18, resulting in a special way of cell death named pyroptosis. In the kidney, NLRP3 inflammasome can be activated by a variety of pathways, which eventually leads to inflammatory infiltration, renal intrinsic cell damage and renal function decline. This paper reviews the function and specific regulatory mechanism of inflammasome in kidney damage caused by various metabolic disorders, which will provide a new therapeutic perspective and targets for kidney diseases.

Relay-based Communications in WBANs

Wireless Body Area Networks (WBANs) constitute an emerging technology in the field of health care that makes health monitoring possible from one’s home itself. WBANs open many challenges by placing sensors on/inside human bodies for collecting various health-related information. Unlike traditional Wireless Sensor Networks (WSNs), communication in WBANs suffers from high channel fading and attenuation due to human body fat. Therefore, relay-based communication with data forwarding techniques is used to handle link failures and poor network connectivity. Accordingly, in this survey article, we present a comprehensive study of relay-based communication mechanisms in WBANs. We begin with a brief look at the multi-tiered architecture of WBANs, how direct communication works, and how relay-based communication is different. Subsequently, we present a detailed review of relay node selection approaches, which, in turn, also affects how a WBAN performs. In this context, we also look at the unique quality of service (QoS) demands of WBANs and how they can be assured.

Brown adipose tissue activation with mirabegron enhances fat oxidation in APOE*3-leiden.CETP mice and humans

Background and Aims: Activation of brown adipose tissue (BAT) increases energy expenditure and reduces body fat in mice and humans. In apoE and LDLR-deficient mice, BAT activation also increases plasma cholesterol, which may suggest that BAT activation might be harmful and promote atherosclerosis. APOE*3-Leiden.CETP mice are a more clinically relevant model for human-like lipoprotein metabolism as they have an intact hepatic apoE-LDLR clearance pathway. The aims of this project were to study the effects of BAT activation by mirabegron on energy expenditure and plasma lipids in APOE*3-Leiden.CETP mice and in humans.

Overweight and obesity among staff of University of Calabar, Calabar, Nigeria

Introduction: Physical inactivity is reported among 41% of Nigerians and 73.8% of adults in Calabar have been reported to be either overweight or obese. Obesity is a chronic disorder marked by excessive generalized deposition and storage of fat in human body. It is indicated by a Body Mass Index of 30kg/m2 and above. The objective of this study was to determine the prevalence of overweight and obesity among the staff of the University of Calabar, Calabar, Nigeria.Methods: A total of 321 staff in University of Calabar participated in this cross sectional study. A multi-stage sampling technique was employed to select faculties, departments, offices and respondents. Data was collected using a semi-structured and self administered questionnaire, a well calibrated weighing scale, a calculator and a checklist. Data analysis was done using IBM Statistical Package for Social Sciences version 20.0.Results: Of the 321 respondents, 55.1% were males and 60.0% were non-teaching. One hundred and twenty nine (40.0%) of the staff were 31-40 years. A total of 43.6% had normal weight, 35.5% were overweight while 19.6% were obese. A total of 45.1% were estimated to be physically inactive and 24.0% did not intend to begin exercises within the next six months. Majority, 91.3% of respondents were knowledgeable about overweight/obesity and 60.4% correctly mentioned at least one possible health implication of overweight/obesity but only 24.3% could define overweight and obesity based on Body Mass Index and most staff (72.0%) believed they had normal weight. Conclusion: The percentage of those found to be either overweight or obese is remarkable and the need to educate staff of the implication and ways to avoid over-nutrition. To avoid the increased risk of developing diabetes and cardiovascular diseases including communicable diseases, preventive health education and regular health checks for staff are recommended.

1977-P: Whole-Exome Sequencing Followed by Functional Analysis to Identify Variants That May Influence Body Mass Index (BMI) via a Role in Adipogenesis

To identify variants that potentially impact human body fat via a role in adipogenesis, we analyzed whole-exome sequence data from a population-based sample of 6809 American Indians with longitudinal measures of BMI. A total of 623,236 exonic variants were detected and those that met the following criteria were prioritized for functional analysis: 1) non-synonymous, stop-gain or frameshift that occurred in ≥5 individuals; 2) a Combined Annotation Dependent Depletion (CADD) score ≥10 (top 10% of deleterious variants); 3) evidence for association with maximum BMI in adulthood (n=6002) or maximum BMI z-score in childhood (n=4882) (P&amp;lt;0.001, adjusted for age, sex, birth year and the first five genetic principal components) and 4) maps to a gene highly expressed in adipose tissue with literature support for a possible role in adipogenesis. The 20 variants which met these criteria had frequency of the BMI-risk allele ranging from 0.0004-0.025 and were characterized in differentiating OP9 cells for a role in lipid accumulation. Variants in PTPRF (P891L), LAMTOR1 (E37K), CCNY (P107R) and ATG5 (I65V) affected triglyceride content, where cells expressing the BMI-risk allele had increased triglycerides as compared to the wild type allele (9.1-20.5%, P=0.05-3x10-4, n=6-10 transfections). Heterozygous carriers for these variants had a higher BMI in adulthood (39.7-54.2 vs. 36.3kg/m2, P=0.05-5x10-4) and/or higher BMI Z-score in childhood (1.2-3.0 vs. 0.3SD, P=0.01-2.1x10-5) as compared to non-carriers. Two of these 4 variants had supportive evidence in other studies; E37K in LAMTOR1 directionally replicated in its association with BMI in GoDarts (P=0.04, n=2902), while I65V in ATG5 associated with waist (P=0.02) or hip circumference (P=0.02) in T2D-GENES (n=12954). In conclusion, whole-exome sequencing followed by in vitro analysis of lipid accumulation in OP9 cells has identified coding variants that may impact BMI via a role in adipogenesis. Disclosure Y.L. Muller: None. S.E. Day: None. C. Koroglu: None. S. Kobes: None. R.L. Hanson: None. W.C. Knowler: None. H. Kim: Employee; Self; Regeneron Pharmaceuticals. C. Van Hout: Employee; Self; Regeneron Genetics Center. N. Gosalia: None. A.R. Shuldiner: Employee; Self; Regeneron Genetics Center. Stock/Shareholder; Self; Regeneron Pharmaceuticals. C. Bogardus: None. L. Baier: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Caloric restriction increases hepatic glucose in obese, insulin‐resistant OLETF rats

Approximately 40% of adults in the United States are classified as obese. Inappropriately elevated body fat in humans contributes to the impairment of insulin signaling, ultimately resulting in alterations to glucose metabolism associated with insulin resistance (IR) and diabetes, both of which are linked to metabolic syndrome (MetS). MetS typically presents with obesity, as a result of overnutrition and a sedentary lifestyle, and causes adverse effects on metabolism, namely on glucose tolerance and insulin response. Caloric restriction (CR) may improve glucose uptake and cellular metabolism, and consistently increases the responsiveness of insulin, resulting in improved insulin sensitivity. The effects of CR on hepatic glycolytic enzymes are not well defined although it is suggested that CR inhibits hepatic glycolysis. More specifically, the effects of CR on hexokinase are not defined. Hexokinase IV (HK IV) catalyzes the first committed step of glycolysis, which is the phosphorylation of glucose to generate glucose‐6‐phosphate (G6P). To evaluate the effect of CR on glucose metabolism and hepatic HK activity during early onset of type 2 diabetes (T2D), sixteen 12‐week old rats were separated into 4 groups (n=4 per group): (1) control strain, LETO, (2) calorically restricted (30%) LETO, (3) obese insulin‐resistant, OLETF, and (4) calorically restricted OLETF. Prior to dissection, an oral glucose tolerance test (oGTT) was performed, and at dissection livers were harvested for measurements of glucose, G6P, and HK activity. Fasting glucose increased with CR in both LETO (63 ± 3 vs 78 ± 2 mg/dL) and OLETF (86 ± 4 vs 92 ± 4 mg/dL). The area under the curve (AUC) for glucose and insulin concentrations were used to estimate the insulin resistance index (IRI). Mean IRI was higher with CR in OLETF (11.7 ± 1.0 vs 13.7 ± 0.89). Hepatic glucose content increased with CR in OLETF (13.2 ± 3.1 vs 17.1 ± 1.0 nmol/μL). Neither hepatic G6P content nor glucose:G6P ratio were significantly changed with CR. While CR improves systemic glucose tolerance and insulin resistance, it increased hepatic glucose content in insulin resistant OLETF rats suggesting that CR inhibits glycolysis via reduced HK activity. Thus, the robust systemic improvements in glucose tolerance with CR during insulin resistant conditions are likely achieved by enhancing peripheral insulin signaling and glucose metabolism.