Fat-rich Diet Research Articles

Influence of Mitochondrial NAD(P) + Transhydrogenase (NNT) on Hypothalamic Inflammation and Metabolic Dysfunction Induced by a High-Fat Diet in Mice.

The mitochondrial protein NAD(P)+ transhydrogenase (NNT) has been implicated in the metabolic derangements observed in obesity. Mice with the C57BL/6J genetic background bear a spontaneous mutation in the Nnt gene and are known to exhibit increased susceptibility to diet-induced metabolic disorders. Most of the studies on NNT in the context of diet-induced obesity have compared C57BL/6J mice with other mouse strains, where differences in genetic background can serve as confounding factors. Moreover, these studies have predominantly employed a high-fat diet (HFD) consisting of approximately 60% of calories from fat, which may not accurately mimic real-world fat-rich diets. In this study, we sought to examine the role of NNT in diet-induced hypothalamic inflammation and metabolic syndrome by using a congenic mice model lacking NNT, along with a HFD providing approximately 45% of calories from fat. Our findings indicate that mice lacking NNT were more protected from HFD-induced weight gain but presented a worse performance on glucose tolerance test, albeit not in insulin tolerance test. Interestingly, the brown adipose tissue of HFD-fed Nnt +/+ mice presented a greater mass and a higher whole-tissue ex-vivo oxygen consumption rate. Also, HFD increased the expression of the inflammatory markers Il1β, Tlr4 and Iba1 in the hypothalamus of Nnt -/- mice. In conclusion, our study highlights the importance of NNT in the context of diet-induced obesity and metabolic syndrome, indicating its contribution to mitigate hypothalamic inflammation and suggesting its role in the brown adipose tissue increased mass.

High-fat and high-sugar diets induce rapid adaptations of fat storage in the house fly Musca domestica L.

Dietary change can be a strong evolutionary force and lead to rapid adaptation in organisms. High-fat and high-sugar diets can challenge key metabolic pathways, negatively affecting other life-history traits and inducing pathologies such as obesity and diabetes. In this study we use experimental evolution to investigate the plastic and evolutionary responses to nutritionally unbalanced diets. We reared replicated lines of larvae of the housefly Musca domestica on a fat-enriched (FAT), a sugar-enriched (SUG), and a control (CTRL) diet for thirteen generations. We measured development time in each generation, and larval growth and fat accumulation in generation 1, 7, and 13. Subsequently all lines were reared for one generation on the control diet to detect any plastic and evolutionary changes. In the first generation, time to pupation decreased on a fat-rich diet and increased on a sugar-rich diet. The fat-rich diet increased fat accumulation and, to a lesser extent, dry weight of the larvae. Multigenerational exposure to the unbalanced diets caused compensatory changes in development time, dry weight, as well as absolute and relative fat content, although pattern and timing depended on diet and trait. When put back on a control diet, many of the changes induced by the unbalanced diets disappeared, indicating that diet has large plastic effects. Nevertheless, fat-evolved lines still grew significantly larger than the sugar-evolved lines, and sugar-evolved lines had consistently lower fat content. This can be an effect of parental diet or an evolutionary change in nutrient metabolism as a consequence of multigenerational exposure to unbalanced diets.

A-068 Development of GIP ELISAs: The Next Level of DiabetesManagement

Abstract Background To develop sensitive and specific ELISAs for the quantitative measurement of total and intact GIP in human plasma, and other biological fluids. Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone consisting of 42 amino acids (1-42aa). This undergoes processing by a dipeptidyl peptidase-4 (DPP-4) and produces GIP (3-42aa) and GIP (3-30aa) fragments. The processed forms have higher affinity and very efficiently inhibits GIP receptor (GIPR) activity with no intrinsic activity. It has also been observed that the GIP response is dependent not only on meal size but also on meal composition. GIP has been found to have physiological and pharmacological relevance in the development of obesity and the pathogenesis of cardiovascular disease besides its involvement in type 2 diabetic pathophysiology. GIP acts in the entero-insular axis as an anabolic hormone that increases insulin levels, which in return increases glycogen and fatty acid synthesis and inhibits the breakdown of fat. GIP also has extra-pancreatic functions as well as roles in the stomach to reduce acid secretion by the parietal cells. On the bone, GIP has a dual effect as it causes the proliferation of osteoblasts as well as inhibits osteoclastic bone resorption. The widespread expression of GIP-R in the brain suggests that GIP might play an essential function in neuro-signaling mechanisms. Methods Highly specific and reproducible total GIP (AL-1013) and Intact GIP (AL-1022) ELISAs have been developed using specific monoclonal antibodies to help estimate the total and intact GIP concentrations in plasma in the respective immunoassays. Results Total and intact GIP ELISAs have been validated using well-characterized sample set and the peptide preparations. The total GIP ELISA detects 1-42aa, 3-42aa, 1-30aa, and 3-30aa in the sample. The intact GIP assay detects GIP (1-42aa) and the most abundant 3-42aa fragment equally in the human plasma. The intact GIP assay does not detect truncated C-terminal fragments(1-30aa). These assays did not cross-react to GRPP, Glucagon, Oxyntomodulin, GLP-1, and GLP-2. Method comparison between intact and total GIP assays using 388 samples yielded a slope of 0.8154 (r=0.958, p < 0.0001). Both the assays are highly reproducible with the total coefficient of variation less than 10%. GIP concentrations were measured in both assays in lean and obese subjects on fat-rich diet at 30-minute intervals. Average concentrations in intact GIP assay at 0 minutes (baseline) in lean and obese subjects (n=10) were 115.6 and 88.5 pg/mL, respectively. Average concentrations in total GIP assay at 0 minutes (baseline) in lean and obese subjects (n=10) were 151.5 and 125.9 pg/mL, respectively. Both total and intact GIP had steep increase in concentrations up to 90 minutes and then flattened up to 180 minutes. The GIP results have been also compared to the mean plasma concentrations of Glucagon, GLP-1, C-Peptide between lean and obese subjects on fat-rich meal. Conclusions Highly sensitive and specific total and intact GIP ELISAs have been developed to reliably quantify these important endocrine and local regulators in physiological and pathophysiological studies for metabolic disorders.

Monounsaturated fat-rich diet reduces body adiposity in women with obesity, but does not influence energy expenditure and substrate oxidation: a parallel randomized controlled clinical trial.

Obesity is an important and growing health problem whose treatment involves dietary changes. In this context, studying the role of macronutrients in weight loss is required in order to understand which strategies may be applied for weight loss. We aimed to evaluate the effects of diets rich in polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on resting energy expenditure (REE), substrate oxidation, and weight loss in women with obesity. Randomized, controlled, single blind, parallel-group clinical trial was conducted for 60 days. Participants (n = 32) were divided into three groups: G1= normocaloric PUFAs-rich diet (12% of total energy expenditure (TEE), 10% of n-6 and up to 2% of n-3); G2= normocaloric MUFAs-rich diet (15-20% TEE); and G3= maintenance of the usual diet. Anthropometric and metabolic variables (REE and substrate oxidation by indirect calorimetry) were evaluated. G2 decreased body weight (-1.92 ± 1.99 kg, P = 0.02), body mass index (BMI) (-0.69 ± 0.70 kg/m2; P = 0.02), waist circumference (WC) (-1.91 ± 1.82 cm; P = 0.02), and body fat (-1.14 ± 1.53 kg; P = 0.04). MUFAs-rich diet reduces body weight, BMI, body fat, and WC. NCT02656940. Clinical Trials: NCT02656940.

Protective effects of niacin following high fat rich diet: an in-vivo and in-silico study

Niacin had long been understood as an antioxidant. There were reports that high fat diet (HFD) may cause psychological and physical impairments. The present study was aimed to experience the effect of Niacin on % growth rate, cumulative food intake, motor activity and anxiety profile, redox status, 5-HT metabolism and brain histopathology in rats. Rats were administered with Niacin at a dose of 50 mg/ml/kg body weight for 4 weeks following normal diet (ND) and HFD. Behavioral tests were performed after 4 weeks. Animals were sacrificed to collect brain samples. Biochemical, neurochemical and histopathological studies were performed. HFD increased food intake and body weight. The exploratory activity was reduced and anxiety like behavior was observed in HFD treated animals. Activity of antioxidant enzymes was decreased while oxidative stress marker and serotonin metabolism in the brain of rat were increased in HFD treated animals than ND fed rats. Morphology of the brain was also altered by HFD administration. Conversely, Niacin treated animals decreased food intake and % growth rate, increased exploratory activity, produced anxiolytic effects, decreased oxidative stress and increased antioxidant enzyme and 5-HT levels following HFD. Morphology of brain is also normalized by the treatment of Niacin following HFD. In-silico studies showed that Niacin has a potential binding affinity with degradative enzyme of 5-HT i.e. monoamine oxidase (MAO) A and B with an energy of ~ − 4.5 and − 5.0 kcal/mol respectively. In conclusion, the present study showed that Niacin enhanced motor activity, produced anxiolytic effect, and reduced oxidative stress, appetite, growth rate, increased antioxidant enzymes and normalized serotonin system and brain morphology following HFD intake. In-silico studies suggested that increase 5-HT was associated with the binding of MAO with Niacin subsequentially an inhibition of the degradation of monoamine. It is suggested that Niacin has a great antioxidant potential and could be a good therapy for the treatment of HFD induced obesity.

The prevalence and risk factors of irritable bowel syndrome (PRIBS study) among adults in low- and middle-income countries: A multicenter cross-sectional study.

Because of the plenty and abundance of risk factors and the expected increase in the prevalence of irritable bowel syndrome (IBS) in the world in general and in low- and middle-income countries in particular, this international cross-sectional study was conducted in 15 low- and middle-income countries according to our previous protocol, NCT05340400. Participants were recruited in the period from April 22, 2022 to June 14, 2022. The diagnosis of IBS was according to ROME IV. We determined the physical activity, daily stress, and fatigue of the participants. A large number of collaborators were chosen from different regions and institutions within each country to achieve diversity within the sample and reduce the probability of bias. The prevalence of IBS appears to be higher in low- and middle-income countries (mean = 25.2%, range [6.2%-44.2%]) than in high-income countries, with a higher prevalence among Africans than Caucasians and Asians. The prevalence of IBS increased in the fourth decade by 32.1% and in the fifth decade by 31.1% (p-value < 0.001). In addition to the previously known risk factors for IBS such as female sex, smoking, psychological stress, and chronic fatigue, other risk factors were discovered such as chronic diseases, including high blood pressure and diabetes, allergies to some substances, previous infection with COVID-19, and the participant having a first-degree relative with a patient. There are also some other modifiable risk factors, such as an abnormal body mass index (whether high or low), smoking, a protein- or fat-rich diet, drinking caffeine-containing beverages, and poor physical activity. Highlighting the prevalence and increasing risk factors of IBS in developing countries should draw the attention of those responsible for health care in these countries and reduce the risk factors.

Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities.

“Perspective of Ischemic Heart Disease (Iqfari Marad-i-Qalb) with reference to Unani Medicine”

Background: Ischemic heart disease (IHD) also known as coronary artery disease (CAD) is the leading cause of death worldwide. IHD is caused by obstruction of one or more coronary arteries. Among the various causes of obstruction atherosclerosis is the leading cause. Physical inactivity, smoking, saturated fat rich diet, hypertension, diabetes mellitus, dyslipidaemia are modifiable risk factors for atherosclerosis which ultimately results in IHD. In this article we will discuss the disease in the light of Unani system of Medicine and how to manage it depending on the understood concepts Methods: A number of classical Unani textbooks were referred for description of various heart diseases and various search engines such as PubMed, Google Scholar and Research Gate were cited for recent advancements using the key words IHD, atherosclerosis, cardio-protective herbal drugs, etc. Conclusion: Owing to the irreversible damage due to IHD it is better to prevent myocardium damage by minimising the risk factors at its earliest. In Unani system of medicine many cardio-protective drugs have been described which when combined with lifestyle modification can play vital role in keeping cardiac diseases at bay. Bangladesh Journal of Medical Science Vol. 22 No. 03 July’23 Page : 475-481

A lipidomics score captures improved dietary fat quality and is related to cardiometabolic risk

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Grant from the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung) to the German Center for Diabetes Research (DZD grant 82DZD00302), Joint Programming Initiative A Healthy Diet for a Healthy Life, as part of the ERA-HDHL cofounded joint call Biomarkers for Nutrition and Health (01EA1704). Background Deep lipidomics might more accurately capture metabolic effects of dietary interventions that aim to modulate the fat quality of the habitual diet compared to standard risk markers. We generated a multi-lipid score (MLS) to summarize the effect of a dietary intervention aiming to substitute saturated with unsaturated fats and assessed its association with incident cardiometabolic diseases. Methods The Dietary Intervention and VAScular function study (DIVAS) was a 16-week, randomized, controlled parallel unsaturated-for-saturated fat substitution (8% total energy, Figure 1A) trial in hundred-thirteen men and women. In regression models, we examined the diet effect on single lipids and combined the significantly affected lipids (P&amp;lt;0.05, multiple testing corrected) in a weighted multi-lipid score (MLS). Then, we used case-cohort designs and Prentice-weighted multi-variable adjusted Cox regression in the European Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort to associate this MLS with primary cardiovascular disease, defined as composite outcome combining stroke and myocardial infarction, and type 2 diabetes (T2D) incidence. Deep lipidomics data (940 molecular lipid species) were available in subsets of both studies (DIVAS: n=113; EPIC-Potsdam: subcohort, n=1262; CVD cases, n=551; T2D cases, n=775). Results The DIVAS unsaturated fat-rich diet reduced lipid metabolites with medium or long-chain fatty acid residuals containing no or few unsaturations in ceramides, cholesterol esters, diglycerides, and phospholipids, which we combine in the MLS (Figure 1B/C). Aside from the MLS, only non-high-density lipoprotein cholesterol (non-HDL-C) was significantly affected in the diet (Figure 1D). In multivariable adjusted models, the MLS, scaled to the observed change in DIVAS (i.e. the theoretical intervention effect), was strongly associated with reduced risk for incident CVD and T2D (Figure 2A). Further adjustment for established risk markers did not meaningfully alter the association, with the exception of the association with T2D and adjustment for plasma triglycerides. Translated to a hypothetical effect on case occurrence, the DIVAS diet intervention-induced MLS difference was associated with markedly fewer CVD (32%, 95%-CI: 21% to 42%) cases and T2D (26%, 95%-CI: 15% to 35%) cases in EPIC-Potsdam (Figure 2B). In contrast, initially observed associations of non-HDL-C, the only other intervention-affected marker, were attenuated when adjusting for the MLS. Conclusion Capturing diet effects using lipidomics profiling, as we show with the generated MLS, might provide superior biomarkers to monitor cardiometabolic benefits of changes to dietary fat quality.

109 Effects of Fat-Rich Nutrients in the Pancreas of an Experimental Burn Model

Abstract Introduction Oversupply of nutrients overstimulates beta cells in standard conditions, and severe burn injuries increase the metabolic needs. In this study, we investigated the effects of fat-rich nutrients on the endocrine pancreas during the acute phase of severe burns. Methods Twenty-one Wistar albino rats were randomly divided into 3 groups. Two groups were fed with standard commercial rat chow (1 with sham procedure and 1 with burn procedure), and the third group (also with burn procedure) was fed a fat-rich diet (60% kcal fat). The burn procedure involved a 25% total body surface area fullthickness burn. Blood samples were taken at 36 hours and 7 days after burn injury or sham procedure. On postburn day 7, skin biopsies were taken and a pancreatectomy was performed. Pancreatic tissues were examined under light microscopy; islets size and cellularity were calculated and investigated immunohistochemically. Results Plasma glucose, C-Peptide, and insulin levels were similar in all the study groups 36 hours and 7 days after burn induction or sham procedure. There was a significant increase in the number of cells per one islet in the burn group given a fat-rich diet compared with the other groups (P = .05). Caspase-3 was strongly expressed in both groups with burn injuries. Conclusions Overconsumption of certain fats can lead to a compensatory response by beta cells that eventually can progress to beta-cell dysfunction during the acute phase of burns. Severe burns induce pancreatic islet cell hyperplasia. Providing excessive fat nutrients during the acute postburn period attenuates this response. Despite the morphophysiological changes observed in the pancreas, all animals in our study achieved similar glycemic homeostasis. Applicability of Research to Practice The delivery of nutritional support is a vital element of burn care, and the main goal is simply to avoid nutritional complications. Lipotoxicity contributes to multisystem organ failure and worse clinical outcomes in obese patients and mice with pancreatitis. Neutralization of IL-1β produces beneficial effects on postburn glycemic control and improves survival. apoptosis in the pancreas of patients with severe burns may be linked to a series of events that can induce Caspase-1 activation and IL-1β release, and these pathways may be influenced by the nutritional status, especially in the early postburn phase. Effective nutritional assessment and management can optimize wound healing and decrease complications and mortality.

Subchronic co-exposure to particulate matter and fructose-rich-diet induces insulin resistance in male Sprague Dawley rats

Insulin resistance (IR) and metabolic disorders are non-pulmonary adverse effects induced by fine particulate matter (PM2.5) exposure. The worldwide pandemic of high fructose sweeteners and fat rich modern diets, also contribute to IR development. We investigated some of the underlying effects of IR, altered biochemical insulin action and Insulin/AKT pathway biomarkers. Male Sprague Dawley rats were subchronically exposed to filtered air, PM2.5, a fructose rich diet (FRD), or PM2.5 + FRD. Exposure to PM2.5 or FRD alone did not induce metabolic changes. However, PM2.5 + FRD induced leptin release, systemic hyperinsulinemia, and Insulin/AKT dysregulation in insulin-sensitive tissues preceded by altered AT1R levels. Histological damage and increased HOMA-IR were also observed from PM2.5 + FRD co-exposure. Our results indicate that the concomitant exposure to a ubiquitous environmental pollutant, such as PM2.5, and a metabolic disease risk factor, a FRD, can contribute to the metabolic disorder pandemic occurring in highly polluted locations.

Exploring body weight-influencing gut microbiota by elucidating the association with diet and host gene expression

We aimed to identify gut microbiota that influences body weight by elucidating the association with diets and host genes. Germ-free (GF) mice with and without fecal microbiota transplant (FMT) were fed a normal, high-carbohydrate, or high-fat diet. FMT mice exhibited greater total body weight; adipose tissue and liver weights; blood glucose, insulin, and total cholesterol levels; and oil droplet size than the GF mice, regardless of diet. However, the extent of weight gain and metabolic parameter levels associated with gut microbiota depended on the nutrients ingested. For example, a disaccharide- or polysaccharide-rich diet caused more weight gain than a monosaccharide-rich diet. An unsaturated fatty acid-rich diet had a greater microbial insulin-increasing effect than a saturated fatty acid-rich diet. Perhaps the difference in microbial metabolites produced from substances taken up by the host created metabolic differences. Therefore, we analyzed such dietary influences on gut microbiota, differentially expressed genes between GF and FMT mice, and metabolic factors, including body weight. The results revealed a correlation between increased weight gain, a fat-rich diet, increased Ruminococcaceae abundance, and decreased claudin 22 gene expression. These findings suggest that weight regulation might be possible through the manipulation of the gut microbiota metabolism using the host’s diet.

Effect of semaglutide and empagliflozin on cognitive function and hippocampal phosphoproteomic in obese mice.

Objective: Based on the 4D label-free phosphoproteomic technique, we examined the differences in cognitive function and hippocampal phosphorylated protein expression in high-fat diet-induced obese mice after the intervention of semaglutide and empagliflozin, as well as the effects of both on protein activity and function in obese mice's hippocampal tissues and the signaling pathways involved. Methods: Thirty-two C57BL/6JC male mice were assigned to two groups randomly: A control group (group C, 10% of energy is from fat, n = 8) and a high-fat diet group (group H, 60% of energy is from fat, n = 24). The high-fat diet-induced obese mice were screened after 12weeks of feeding based on the criterion that the bodyweight of mice in fat rich diet group was greater than or equal to 20% of the average body weight of the mice in the blank control group. Group H separate into group H (n = 8), group Semaglutide (group S, n = 8), and group empagliflozin (group E, n = 8). For a total of 12weeks, group S received 30nmol/kg/d bodyweight of semaglutide intraperitoneally, group E received 10mg/kg/d bodyweight of empagliflozin via gavage, and groups C and H received equal amounts of saline by intraperitoneal injection and gavage. At the end of treatment, the mice were appraised for cognitive function employing the Morris water maze (MWM), and serum fasting glucose, lipids, and inflammatory parameters were measured. The 4D label-free phosphoproteomics method was employed to screen the differential phosphoproteins and loci in hippocampal tissues of mice in different treatment groups, and bioinformatics was used to analyze the biological processes, signaling pathways, and related protein-protein interaction (PPI) network analysis of these differentially phosphorylated proteins. Results: In comparison to normal controls, The escape latency of obese mice induced by high-fat diet was prolonged, the percentage of swimming time in the target quadrant was reduced, and the number of times of crossing the platform was reduced, whereas semaglutide and empagliflozin treatment reduced escape latency, increase the percentage of swim time in the target quadrant and increase the frequency of passing through the platform area, although there is little difference in the effect of the two drugs. The phosphoproteomic results showed 20,493 unique phosphorylated peptides, representing 21,239 phosphorylation sites and 4,290 phosphorylated proteins. Further analysis revealed that the proteins corresponding to these differentially phosphorylated sites are jointly distributed in signaling pathways such as dopaminergic synapses and axon guidance, and are involved in biological processes such as neuronal projection development, synaptic plasticity, and axonogenesis. Notably, the key factors voltage-dependent L-type calcium channel subunit alpha-1D (CACNA1D), voltage-dependent P/Q-type calcium channel subunit alpha-1A (CACNA1A), and voltage-dependent N-type calcium channel subunit alpha-1B (CACNA1B) were all found to be involved in the dopaminergic synapse pathway, and their expression was upregulated by semaglutide and empagliflozin. Conclusion: We found for the first time that a high-fat diet decreased CACNA1D, CACNA1A, and CACNA1B protein serine phosphorylation, which may affect neuronal development, synaptic plasticity, and cognitive function in mice. Notably, semaglutide and empagliflozin increased the phosphorylation of these proteins.

Histological and Microscopic Analysis of Fats in Heart, Liver Tissue, and Blood Parameters in Experimental Mice.

The intake of various types and amounts of dietary fats influences metabolic and cardiovascular health. Hence, this study evaluated the impact of routinely consumed Pakistani dietary fats on their cardiometabolic impact. For this, we made four groups of mice, each comprising 5 animals: (1) C-ND: Control mice on a normal diet, (2) HFD-DG: High-fat diet mice on a normal diet plus 10% (w/w) desi ghee, (3) HFD-O: Mice on normal diet plus 10% (w/w) plant oil (4) HFD-BG: Mice on normal diet plus 10% (w/w) banaspati ghee. Mice were fed for 16 weeks, and blood, liver, and heart samples were collected for biochemical, histological, and electron microscopic analysis. The physical factors indicated that mice fed on HFD gained more body weight than the C-ND group. Blood parameters do not show significant differences, but overall, the glucose and cholesterol concentrations were raised in the mice fed with a fat-rich diet, with the highest concentrations in the HFD-BG group. The mice fed with HFD-BG and HFD-O had more lipid droplets in the liver, compared to HFD-DG and C-ND.

Study of Association of Dietary Factors with Severity of Acute Pancreatitis

Objective: To determine the association of dietary factors with severity of acute pancreatitis (AP). Materials and Methods: A total of 250 patients who presented in General Surgery unit from Jan-2022 to Dec-2022 were included. Data regarding etiology of AP and demographics of patients was obtained. A special questionnaire was designed to obtain information regarding the dietary habits of patients based on different types of diet. The questionnaire included information regarding use of meat, fat in daily diet, dairy products use, and desserts use. Results: Mean age of study patients was 48.3±18.5 years. Majority were females, 135 (54%) were females and 115 (46%) were males. There was significant association of meat rich diet and fat rich diet with severity of AP, 81 (60.9%) patients of mild AP had main diet as meat, 47 (68.1%) in moderate AP group and 40 (83.3%) in severe AP group had main diet as meat (p-value 0.01). 15 (11.3%) patients in mild AP, 11 (15.9%) in moderate AP and 13 (27.1%) in severe AP group reported to have use high fat usage in daily diet (p-value 0.03). Conclusion: Meat rich and fat rich diets are independently associated with severe AP. So modification of diet in-terms of reduction in meat and fat and addition of fibrous food in daily diet can help to reduce in incidence and severity of AP in high risk patients. Keywords: Acute Pancreatitis, dietary factors, disease severity, meat, fat.

Lipid Profile Changes Among Male and Female Regarding their Body Mass Index and Diet a Comparative Cross-Sectional Study

Objective: The hypothesis that body mass index and diet has direct influence on plasma lipids. The aims and objectives of present study were to highlight the relationship between, BMI, diet and components of lipid profile in male and female individuals. Study Design: This was a cross-sectional comparative study in which blood samples were collected from both male and female individuals. Place and Duration: Present study was conducted in medical units of Jinnah hospital Lahore, Services hospital Lahore and Bahawal Victoria hospital Bahawalpur from February 2022 to November 2022. Methodology: Total 500 individuals were divided into different groups such as Group-A with 100 normal individuals were control while in Group-B 100 male individuals of 30-45 years with low fat balanced diet, in Group-C 100 male individuals with fat rich imbalanced diet, in Group-D 100 female individuals of 30-45 years with low fat balanced diet whereas in Group-E 100 female individuals with fat rich imbalanced diet were selected and BMI, Cholesterol, Triglyceride, LDL and HDL levels were measured respectively. Results: The findings of present study indicated different levels of cholesterol, triglycerides, low density lipoproteins and high density lipoproteins with comparative significant (P≤0.05) changes in different groups as compared with control Group-A. A remarkable changes in cholesterol, triglycerides, LDL, HDL levels in Group-B and Group-C were seen (160.1±0.02, 112.1±0.01, 106.1±0.01, 40.1±0.01) (210.2±0.01, 152.1±0.02, 120.2±0.03, 37.4±0.01) respectively. While in Group-E as compared with Group-D the cholesterol, triglycerides, LDL, HDL levels (230.2±0.04, 192.1±0.02, 130.1±0.01, 42.1±0.02) (170.2±0.04, 112.1±0.02, 110.2±0.03, 50.4±0.01) were high as compared with the individuals of Group-D. Practical implication: The regular health awareness programs were not available for local population from health administration while lipid profile is directly proportional to the cardiac medical complications in all over the world. The main task of present study was to provide exact medical awareness to the people about diet related variations of cholesterol, triglycerides, LDL and HDL levels and ultimately it was concluded that dyslipidemia can occur in those with a normal BMI as well as those who are obese or overweight. Conclusion: The findings of current study were described that cholesterol, triglycerides, LDL and HDL levels have correlation with BMI and intake diet. Therefore comparative significant (P≤0.05) changes in fat rich imbalanced groups were seen as compared with low fat balanced diet groups. According to the findings of this study, dyslipidemia can occur in those with a normal BMI as well as those who are obese or overweight. Keywords: Body mass index, Cholesterol, Triglycerides, Low density lipoproteins, High density lipoproteins

Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy.

Dietary habits contribute to the characteristics of Alzheimer's disease (AD) and cognitive impairment, which are partly induced by the accumulation of hyperphosphorylated Tau, a microtubule-associated protein. In mice, a fat-rich diet facilitates cognitive dysfunction. However, the mechanism by which dietary fat damages the brain remains unclear. In this study, 13-month-old C57BL/6 mice were fed a normal or high-fat diet (HFD) for 6 months. Neuro-2a cells were incubated with the normal medium or palmitic acid (200 μM). Spatial memory was assessed utilizing a behavioral test. Further, western blotting and immunofluorescence techniques were used to determine the levels of mitophagy-related proteins. The synaptic morphology and phosphorylation of Tau proteins were also evaluated. Administration of HFD decreased the expression of synaptophysin and brain-derived neurotrophic factor expression, leading to significant damage to neurons. Tau protein hyperphosphorylation was detected at different loci both in vivo and in vitro. Significantly impaired learning and memory abilities, accompanied by impaired mitophagy-related processes, were observed in mice fed with HFD as compared to mice fed with normal food. In conclusion, high fatty-acid intake hinders mitophagy and upregulates Tau protein phosphorylation, including age-related synaptic dysfunction, which leads to cognitive decline.

Genetic Val66Met BDNF Variant Increases Hyperphagia on Fat-rich Diets in Mice.

High prevalence of obesity is attributable in part to consumption of highly palatable, fat-rich foods. However, the mechanism controlling dietary fat intake is largely unknown. In this study we investigated the role of brain-derived neurotrophic factor (BDNF) in the control of dietary fat intake in a mouse model that mimics the common human Val-to-Met (Val66Met) polymorphism that impairs BDNF release via the regulated secretory pathway. BdnfMet/Met mice gained weight much faster than wild-type (WT) mice and developed severe obesity due to marked hyperphagia when they were fed HFD. Hyperphagia in these mice worsened when the fat content in their diet was increased. Conversely, mice lacking leptin exhibited similar hyperphagia on chow and HFD. When 2 diets were provided simultaneously, WT and BdnfMet/Met mice showed a comparable preference for the more palatable diet rich in either fat or sucrose, indicating that increased hyperphagia on fat-rich diets in BdnfMet/Met mice is not due to enhanced hedonic drive. In support of this interpretation, WT and BdnfMet/Met mice increased calorie intake to a similar extent during the first day after chow was switched to HFD; however, WT mice decreased HFD intake faster than BdnfMet/Met mice in subsequent days. Furthermore, we found that refeeding after fasting or nocturnal feeding with HFD activated TrkB more strongly than with chow in the hypothalamus of WT mice, whereas TrkB activation under these 2 conditions was greatly attenuated in BdnfMet/Met mice. These results indicate that satiety factors generated during HFD feeding induce BDNF release to suppress excess dietary fat intake.

Effects of Zhishi Daozhi Decoction on the intestinal flora of nonalcoholic fatty liver disease mice induced by a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

Pathological and biochemical investigation of the effects of l-carnitine and gemfibrozil on peroxisome proliferator activated Receptors (PPARS) and lipidosis in rabbits on a high-fat diet

Obesity and fatty liver is a widespread growing health problem in human with detrimental consequences that encouraged researchers to find ways to overcome it. In this study, gemfibrozil and L-carnitine were evaluated in prevention of obesity and hepatic lipidosis also the role of L-carnitine in avoiding side effects of gemfibrozil was investigated. The study involved 56 New-Zealand Albino rabbits, divided into 2 main groups and then subdivided into 4 equal groups (n=7). The groups I (normal diet), II (normal diet+gemfibrozil), III (normal diet+L-carnitine) and IV (normal diet+gemfibrozil+L-carnitine) received normal diet and the groups V (fat rich diet), VI (fat rich diet+gemfibrozil), VII (fat rich diet+L-carnitine) and VIII (fat rich diet+gemfibrozil+L-carnitine) received fat rich diet for 8 weeks. Animals were blood sampled and wieght weekly during the experiment and at the end of the experiment for determination of biochemical (HDL, High-density lipoproteins; LDL, Low-density lipoprotein; VLDL, Very low-density lipoprotein; ALT, Alanine amino transferase; AST, Aspartate aminotransferase; GGT, Gamma glutamyltransferase; GLDH, Glutamate lactate dehydrogenase; LDH, Lactate dehydrogenase) and oxidative stress (MDA, Malondialdehyde; GSH, Reduced gluthation; NO, Nitric oxide; SOD, Superoxide dismutase) parameters. All rabbits were euthanised for histopathological examination and for distrubition of Peroxisome proliferator activated receptors (PPARs) in tissues by immunohystochemistry. Liver enzymes increased in fat rich diet group throughout the study. Addition of gemfibrozil and L-carnitin in fat rich diet resulted in statistically significant decreasein lipid profile when compared to those only received fat rich diet. Beta oxidation of fat rich diet group was significantly higher than that of groups additionally received gemfibrozil and L-carnitine. Immunohistochemistry revealed an increase in PPAR PPAR-α and β but not PPAR-γ expression in fat rich diet group. On the contrary L-carnitin administration did have any effect on tissue PPAR expression. PPAR-α expression differed between groups received gemfibrozil and fat rich diet and those did not. Fat rich diet increased MDA level while decreased GSH and catalase. Addition of gemfibrozil and L-carnitine to fat rich diet significantly decreased MDA level and increased antioxidants. The most marked macroscopy finding was abdominal fat increase in fat rich diet group (group V). On the other hand gemfibrozil administration resulted in significant abdominal fat decrease. Furthermore decreased abdominal fat was marked in gemfibrozil and L-carnitine given animals (group VIII) when compared to other groups. In conclusion, gemfibrozil and L-carnitine administration alleviated abdominal and hepatic fattening and improved lipid profile. Gemfibrozil also caused a significant increase in PPAR-α expression in the liver. It may be of use in avoiding abdominal fat (obesity) due to high fat by use of gemfibrozil, a synthetic PPAR-a ligand, and L-carnitine.