Ectopic Fat Deposition Research Articles

Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice.

The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Euglena Attenuates High-Fat-Diet-Induced Obesity and Especially Glucose Intolerance.

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods.

Steatosarcopenia: A New Terminology for Clinical Conditions Related to Body Composition Classification.

Body composition analysis focuses on measuring skeletal muscle mass and total body fat. The loss of muscle function and mass is related to clinical conditions such as frailty, increased risk of falls, and prolonged hospitalizations. Despite the relevance of the definition of sarcopenic obesity, there is still a gap in the monitoring of patients who have the combination of sarcopenia and myosteatosis, regardless of the presence of obesity. Therefore, we propose a new nomenclature, steatosarcopenia, a condition characterized by the loss of mass or skeletal muscle strength and performance associated with the excessive deposition of ectopic reserve fat in muscle tissue, in the same individual, not necessarily related to excess fat total body mass. A greater understanding of this condition may assist in developing strategies for preventing and treating metabolic diseases.

Acupuncture-assisted lifestyle intervention improve the metabolic status and spontaneous brain activity of type 2 diabetes Mellitus patients: a randomized, clinical trial

BackgroundAggressive weight management in patients with type 2 diabetes mellitus has demonstrated numerous metabolic advantages, however, existing therapies for weight control have not reached satisfactory results. This study aimed to evaluate the efficacy and safety of acupuncture in the weight management of type 2 diabetes mellitus (T2DM) patients by using a randomized, sham-controlled clinical trial design.MethodsIn this single-blind randomized clinical trial, 102 overweight adult T2DM patients were randomized into two groups. The control group receives diet, exercise, and sham acupuncture intervention, whereas the acupuncture group receives diet and exercise and acupuncture intervention, both for 1 month. Body weight and other anthropometric and laboratory indices were assessed at baseline and endpoint, meanwhile, the body fat content and spontaneous brain activity were measured by functional magnetic resonance imaging(fMRI)as the exploratory outcomes.ResultsNo significant difference was observed between the studied parameters at the baseline. The body weight and BMI were significantly reduced both in the control and acupuncture groups after intervention, without statistical difference between the two groups. What’s interesting is that compared to the control, the acupuncture group displayed a greater improvement in central fat tissue. It notes that the acupuncture group achieved significant liver fat content reduction than the sham acupuncture group. At the same time, the spontaneous brain activity in the occipital lobe and parietal lobe significantly increased in the acupuncture group.ConclusionOne month of acupuncture treatment preferentially improved ectopic fat deposition and was accompanied by changes in brain activity compared with the control group, even before significant changes in total body weight had occurred. further studies of longer duration are necessary for validation.Trial registration: The protocol of this clinical trial is registered at the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR, http://www.acmctr.org/, No. AMCTR-IOR-20000341).

7785 Muscle Strength and Physical Performance Are Closely Related to Muscle Quality Regardless of Muscle Mass or Diabetes Status

Abstract Disclosure: J. Seo: None. I. Jung: None. S. Park: None. D. Lee: None. J. Yu: None. H. Cho: None. K. Kim: None. E. Song: None. K. Kim: None. N. Kim: None. H. Yoo: None. S. Kim: None. K. Choi: None. N. Kim: None. C. Shin: None. Weakness or slowness is essential to define sarcopenia rather than less muscle mass. Myosteatosis is associated with low muscle strength and poor physical performance, and ectopic fat deposition is a characteristic of diabetes (DM). We investigated the association between muscle strength/physical performance and myosteatosis by considering DM status and muscle mass in community-dwelling older adults. A total of 982 subjects (447 men and 535 women) aged 54-83 years in 8th examination of the Korean Genome and Epidemiology Study Ansan cohort participated in this study. Handgrip strength (HSG), 4-m walking velocity (VEL) and 30-Seconds Sit-to-Stand Test (STST) were checked, appendicular skeletal muscle mass (ASM) and total muscle mass (TMM) by DXA were measured. In midthigh CT image, total muscle area (TMA) was measured and categorized into 3 components using Hounsfield Unit (HU): normal-attenuation muscle area (NAMA, 35-100HU), low-attenuation muscle area (LAMA, 0-34HU), and inter/intramuscular adipose tissue (IMAT) area. As muscle quality indices, the NAMA index, LAMA index, and IMAT index were defined by dividing each parameter by TMA. DM was diagnosed by fasting glucose ≥126 mg/dL, 2hr-OGTT glucose ≥200 mg/dL, HbA1c ≥6.5% or anti-diabetic medication. Subjects with DM (38% of total subjects) had higher age and body mass index (BMI) compared to non-DM subjects. Prevalence of low muscle mass (M:<7.0kg/m2, F:<5.4kg/m2 of ASM/height2) was not statistically different by the presence of DM (DM vs non-DM, 11.7% vs 9.7% in men, 3.6% vs 7.6% in women). However, prevalence of low HGS (M:<28kg, F:<18kg) and slow VEL (<1.0m/sec) was higher in DM subjects than non-DM subjects (DM vs non-DM, low HSG: 18.3% vs 5.6% in men, 28.0% vs 17.3% in women, slow VEL: 40.6% vs 30.7% in men, 61.7% vs 46.2% in women). After adjusting for age and BMI, men with DM had lower muscle mass (ASM, ASM/height2,), TMA and NAMA index but higher LAMA index and IMAT index compared to men without DM. Also, men with DM had lower HGS (p=0.001) and poor STST (p=0.008) than men without DM. In women, muscle mass and muscle quality indices were not significantly different with or without DM, but women with DM had worse STST than women without DM (p=0.013). Age and sex adjusted HSG, but not VEL and STST, was positively associated with muscle mass (ASM, ASM/height2, ASM/BMI, and TMM). Age and sex adjusted HSG, VEL, and STST were positively associated with NAMA index and negatively associated with LAMA index and IMAT index regardless of DM. Linear regression analysis revealed that both ASM and NAMA (or LAMA) indices were independent association factors for HGS. Subjects with DM showed a more pronounced decrease in physical performance and muscle strength than a decrease in muscle mass. In this population-based cohort, less myosteatosis was associated with greater muscle strength and better physical performance, regardless of muscle mass or DM status. Presentation: 6/2/2024

Effects of Glucagon-Like Peptide 1 Agonists (GLP-1 RAs) on Ectopic Fat Deposition in CKD: A Pilot and Feasibility Study (GLIMP)

Effects of Glucagon-Like Peptide 1 Agonists (GLP-1 RAs) on Ectopic Fat Deposition in CKD: A Pilot and Feasibility Study (GLIMP)

Impact of Sex on the Therapeutic Efficacy of Rosiglitazone in Modulating White Adipose Tissue Function and Insulin Sensitivity.

Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic target. Rosiglitazone (RSG), a potent PPARγ agonist, promotes healthy WAT growth and mitochondrial function through MitoNEET modulation. Recent RSG-based strategies specifically target white adipocytes, avoiding side effects. Our aim was to investigate whether sex-specific differences in the insulin-sensitizing effects of RSG exist on WAT during obesity and inflammation. We used Wistar rats of both sexes fed a high-fat diet (HFD, 22.5% fat content) for 16 weeks. Two weeks before sacrifice, a group of HFD-fed rats received RSG treatment (4 mg/kg of body weight per day) within the diet. HFD male rats showed greater insulin resistance, inflammation, mitochondrial dysfunction, and dyslipidemia than females. RSG had more pronounced effects in males, significantly improving insulin sensitivity, fat storage, mitochondrial function, and lipid handling in WAT while reducing ectopic fat deposition and enhancing adiponectin signaling in the liver. Our study suggests a significant sexual dimorphism in the anti-diabetic effects of RSG on WAT, correlating with the severity of metabolic dysfunction.

Body Composition, Sarcopenia, and Serum Myokines in Acromegaly: A Narrative Review.

Patients with active acromegaly have a higher percentage of lean body mass, a lower percentage of fat body mass, and an increase in their extracellular water compartment compared to healthy individuals. However, muscle function appears to be compromised in patients with acromegaly, with some experiencing worsened physical performance and sarcopenia. Myokine alterations, insulin resistance, dysregulation of protein metabolism, muscle oxidative stress, neuromuscular junction impairment, and increased ectopic intramuscular fat deposits may play roles in muscle dysfunction in patients with acromegaly.

Association of Insulin Resistance and Ectopic Fat Accumulation with HOMA Indices: A Single-Centre Observational Study

Purpose: The aim of this study was to investigate the relationship between non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas (or pancreatic) disease (NAFPD) and HOMA indices in obese patients without a diagnosis of diabetes mellitus, using ultrasound (US) as a common non-invasive diagnostic tool during routine examinations. Methods: In this single-centre, retrospective study, the records of patients who applied to the obesity outpatient clinic in 2023 were reviewed. Digital records were scanned and patients with abdominal ultrasound reports indicating age, gender, body mass index(BMI), fasting plasma glucose, fasting plasma glucose, C-peptide level and degree of pancreatic and hepatic steatosis were included in the study. Patients with known chronic disease or diabetes mellitus and patients with specific drug use were excluded from the study. Homa indices were calculated using fasting plasma glucose and C-peptide levels. Results: A total of 62 patients were included. Body mass index was 39.1, 91% had NAFLD and 82% had NAFPD. There was a significant positive correlation between BMI and NAFLD and NAFPD. HOMA scores revealed a statistically significant impact of NAFLD on insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-S) but not on beta-cell function (HOMA-B). No significant effect of NAFPD on HOMA scores was observed. Conclusion: The findings underline the association between NAFLD and insulin resistance and highlight the metabolic burden of ectopic fat deposition in obese patients. In contrast, there was no significant correlation between NAFPD and either insulin resistance or beta-cell function, suggesting that the metabolic impact of pancreatic steatosis may be different. These findings may help to guide clinical strategies for detecting and treating metabolic disorders in obesity.

The Effects of Exercise Interventions on Ectopic and Subcutaneous Fat in Patients with Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = -2.502 kg, p = 0.001], liver fat% [WMD = -1.559%, p = 0.030], VFA [SMD = -0.510, p = 0.001], and SFA [SMD = -0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health.

Ethnic differences in the relationship between ectopic fat deposition and insulin sensitivity in Black African and White European men across a spectrum of glucose tolerance.

To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue-specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men. Fifty-three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two-step hyperinsulinaemic-euglycaemic clamp with infusion of D-[6,6-2H2]-glucose and [2H5]-glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL). Associations between ectopic fat and IR were assessed using linear regression models. There were no differences in tissue-specific IR between ethnic groups at any stage of glucose tolerance. VAT level was consistently lower in the BA population; NGT (p = 0.013), IGT (p = 0.006) and T2D (p = 0.015). IHL was also lower in the BA compared with the WE men (p = 0.013). VAT and IHL levels were significantly associated with hepatic IR in the BA population (p = 0.001) and with peripheral IR in the WE population (p = 0.027). The present study suggests that BA and WE men exhibit the same degree of IR across a glucose tolerance continuum, but with lower VAT and IHL levels in the BA population, suggesting that IR may be driven by a mechanism other than increased ectopic fat accumulation in BA men.

Adipose tissue-liver cross-talk: a route to hepatic dysfunction in pregnant women with obesity.

Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity.

High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients.

Lipid metabolism imbalance is involved in the mechanism of renal tubular injury in diabetic kidney disease (DKD). Fatty acid binding protein 4 (FABP4) has been reported to participate in cellular lipid toxicity. However, the expression of FABP4 in renal tissues of DKD and its correlation with clinical/ pathological parameters and prognosis have not been studied. A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis. DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD. High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Adipose-derived extracellular vesicles - a novel cross-talk mechanism in insulin resistance, non-alcoholic fatty liver disease, and polycystic ovary syndrome.

Obesity is the best described risk factor for the development of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) while the major pathogenic mechanism linking these entities is insulin resistance (IR). IR is primarily caused by increased secretion of proinflammatory cytokines, adipokines, and lipids from visceral adipose tissue. Increased fatty acid mobilization results in ectopic fat deposition in the liver which causes endoplasmic reticulum stress, mitochondrial dysfunction, and oxidative stress resulting in increased cytokine production and subsequent inflammation. Similarly, IR with hyperinsulinemia cause hyperandrogenism, the hallmark of PCOS, and inflammation in the ovaries. Proinflammatory cytokines from both liver and ovaries aggravate IR thus providing a complex interaction between adipose tissue, liver, and ovaries in inducing metabolic abnormalities in obese subjects. Although many pathogenic mechanisms of IR, NAFLD/MASLD, and PCOS are known, there is still no effective therapy for these entities suggesting the need for further evaluation of their pathogenesis. Extracellular vesicles (EVs) represent a novel cross-talk mechanism between organs and include membrane-bound vesicles containing proteins, lipids, and nucleic acids that may change the phenotype and function of target cells. Adipose tissue releases EVs that promote IR, the development of all stages of NAFLD/MASLD and PCOS, while mesenchymal stem cell-derived AVs may alleviate metabolic abnormalities and may represent a novel therapeutic device in NAFLD/MASLD, and PCOS. The purpose of this review is to summarize the current knowledge on the role of adipose tissue-derived EVs in the pathogenesis of IR, NAFLD/MASLD, and PCOS.

Associations of adipose insulin resistance index with leg (gluteofemoral) fat (inverse) and serum alanine aminotransferase (positive) in young Japanese women

AimAssociations of the adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acid) with body fat distribution and the ratio of alanine to aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, were examined in the context of the metabolic syndrome. MethodsLegs, the trunk and body fat by DXA, blood pressure (BP) and blood chemistry were measured in 284 young Japanese female university students and 148 middle-aged biological mothers whose BMI averaged <23 kg/m2. ResultsYoung women had higher leg fat/body fat and lower trunk fat/body fat ratio (both p < 0.001) compared with middle-aged women but AT-IR did not differ between the two groups. We had multivariable linear regression analysis for AT-IR as a dependent variable including leg fat/body fat ratio, trunk fat/body fat ratio, fasting glucose, triglyceride, HDL cholesterol and systolic BP as independent variables. Leg fat/body fat ratio, fasting glucose and triglyceride (p = 0.013, 0.009 and 0.016, respectively) emerged as determinants of AT-IR in young women. Trunk fat/body fat ratio and fasting glucose (p = 0.003 and 0.019, respectively) emerged in middle-aged women. In a model which included ALT/AST as an additional independent variable, ALT/AST (p = 0.016) was the fourth independent determinant in young women and the single determinant of AT-IR in middle-aged women (p < 0.001). ConclusionIn young Japanese women, adipose tissue insulin resistance was associated with reduced leg fat, a subtle partial lipodystrophy-like phenotype associated with reduced adipose tissue expandability. It was associated with elevated trunk (abdominal) fat in middle-aged women and with ALT/AST, a marker of hepatosteatosis, in two groups of Japanese women, suggesting ectopic fat deposition associated with reduced adipose tissue expandability.

Does the Location of Fat Accumulation Affect the Degree of Aortic and Renal Arterial Calcification?

The vascular risk associated with obesity is particularly associated with visceral adiposity, but recent studies suggest that ectopic fat might contribute to the increased risk of atherosclerotic cardiovascular disease. Our study aimed to explore the connection between arterial calcification of the aorta and renal arteries with visceral and ectopic fat deposits, including liver, pancreatic, and renal sinus fat. Retrospective analysis of thoracoabdominal multi-slice computed tomography (MSCT) scans of 302 patients included measurements of calcification volumes of thoracic and abdominal aorta, and of both renal arteries. On the same scans, the visceral fat volume, liver-to-spleen ratio, pancreatic-to-spleen ratio, and both renal sinus fat areas were retrieved. Logistic regression showed the left kidney sinus fat area to be the most strongly associated with calcifications in the aorta and both renal arteries (coef. from 0.578 to 0.913, p < 0.05). The visceral fat positively predicted aortic calcification (coef. = 0.462, p = 0.008), and on the contrary, the pancreatic fat accumulation even showed protective effects on thoracic and abdominal aorta calcification (coef. = -0.611 and -0.761, p < 0.001, respectively). The results suggest that ectopic fat locations differently impact the calcification of arteries, which should be further explored.

Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

Subtherapeutic Kitasamycin Promoted Fat Accumulation in the Longissimus Dorsi Muscle in Growing-Finishing Pigs.

Kitasamycin (KM), a broad-spectrum macrolide antibiotic, has implications for growth performance and residue in animals and humans. This study aimed to explore the effects of different KM doses on intramuscular fat accumulation, cecal microflora, and short-chain fatty acids (SCFAs) using a growing-finishing pig model. Forty-two pigs were divided into three groups: control, subtherapeutic KM (50 mg/kg, KM50), and therapeutic KM (200 mg/kg, KM200) diets over 8 weeks. KM50 led to increased back fat thickness, fat content in the longissimus dorsi muscle (LM), and elevated plasma total cholesterol (TC) levels (p < 0.05), supported by upregulated lipid synthesis gene expression (Acc1, Fas, Scd1) (p < 0.05) in the LM. KM50 altered cecal microflora, reducing Lactobacillus spp. and Bifidobacterium spp. abundance, while increasing SCFA concentrations (acetic acid, propionic acid, total SCFAs) (p < 0.05). KM200 had minimal effects on intestinal weight and density, with increased apparent digestibility of nutrients. These findings highlight the dose-dependent impact of KM on intramuscular fat deposition. Subtherapeutic KM induced ectopic fat deposition, emphasizing potential risks in disease treatment for humans and animals.

Complex insoluble dietary fiber alleviates obesity and liver steatosis, and modulates the gut microbiota in C57BL/6J mice fed a high-fat diet.

Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.

The interplay between diabetes and non-alcoholic fatty liver disease: a cross-sectional study from Pakistan.

Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels. This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups. The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008). There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.