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.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Changes in Visceral and Ectopic Adipose Tissue Stores Across Pregnancy and Their Relationship to Gestational Weight Gain.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearson's correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P < 0.001), SAT (r = 0.74; P < 0.001), and VAT (r = 0.63; P < 0.001) but not significantly correlated with changes in ectopic lipids (IHL, IMCL, and EMCL; -0.14 < r < 0.26). CONCLUSIONS: Preferential deposition of adipose tissue to the viscera in pregnancy, as seen in our sample, could serve an important metabolic function; however, excessive deposition in this region could negatively affect maternal health.

Impact of a Mediterranean diet on hepatic and metabolic outcomes in non-alcoholic fatty liver disease: The MEDINA randomised controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is predominantly managed by lifestyle intervention, in the absence of effective pharmacotherapies. Mediterranean diet (MedDiet) is the recommended diet, albeit with limited evidence. AIMS: To compare an ad libitum MedDiet to low-fat diet (LFD) in patients with NAFLD for reducing intrahepatic lipids (IHL) by proton magnetic resonance spectroscopy (1 H-MRS). Secondary outcomes include insulin resistance by homeostatic model of assessment (HOMA-IR), visceral fat by bioelectrical impedance analysis (BIA), liver stiffness measurement (LSM) and other metabolic outcomes. METHODS: In this parallel multicentre RCT, subjects were randomised (1:1) to MedDiet or LFD for 12 weeks. RESULTS: Forty-two participants (25 females [60%], mean age 52.3 ± 12.6 years) were included, 23 randomised to LFD and 19 to MedDiet.; 39 completed the study. Following 12 weeks, there were no between-group differences. IHL improved significantly within the LFD group (-17% [log scale]; p = .02) but not within the MedDiet group (-8%, p = .069). HOMA-IR reduced in the LFD group (6.5 ± 5.6 to 5.5 ± 5.5, p < .01) but not in the MedDiet group (4.4 ± 3.2 to 3.9 ± 2.3, p = .07). No differences were found for LSM (MedDiet 7.8 ± 4.0 to 7.6 ± 5.2, p = .429; LFD 11.8 ± 14.3 to 10.8 ± 10.2 p = .99). Visceral fat reduced significantly in both groups; LFD (-76% [log scale], p = <.0005), MedDiet (-61%, p = <.0005). CONCLUSIONS: There were no between-group differences for hepatic and metabolic outcomes when comparing MedDiet to LFD. LFD improved IHL and insulin resistance. Significant improvements in visceral fat were seen within both groups. This study highlights provision of dietary interventions in free-living adults with NAFLD is challenging.

Higher dietary protein intake preserves lean body mass, lowers liver lipid deposition, and maintains metabolic control in participants with long-chain fatty acid oxidation disorders.

Medical nutrition therapy for long-chain fatty acid oxidation disorders (LC-FAODs) currently emphasizes fasting avoidance, restricted dietary long-chain fatty acid intake, supplementation with medium chain triglycerides, and increased carbohydrate intake. We hypothesize that increasing dietary protein intake relative to carbohydrate intake would preserve metabolic control yet induce physical benefits including reduced hepatic lipogenesis. Therefore, we compared two dietary approaches with similar fat intake but different carbohydrate to protein ratios in participants diagnosed with LC-FAODs. Thirteen participants were enrolled and randomized into either a high-protein (PRO) or a high-carbohydrate (CHO) diet for 4 months. Baseline and 4-month assessments included body composition, ectopic lipid deposition, and resting energy expenditure. End of study assessments also included total energy expenditure, metabolic responses to oral feedings, and whole-body fatty acid oxidation capacity. At the end of the dietary intervention, both groups had similar energy expenditure, fat and glucose oxidation rates, and glucolipid responses to mixed meal and oral glucose loads. Neither dietary group experienced worsening symptoms related to their LC-FAOD. Compared to the CHO group, the PRO group exhibited increased blood levels of short-chain acylcarnitines, reduced intrahepatic lipid content, and maintained lean body mass while the CHO group lost lean mass. In patients with LC-FAODs, increasing protein intake maintained metabolic control, reduced liver fat without risk of metabolic decompensation, and helped preserve lean body mass. We propose that a modest increase in dietary protein along with fasting avoidance and fat restriction may improve body composition and energy expenditure in patients with LC-FAODs.

Sex Differences in Body Composition.

Body composition differs between men and women. Men have more lean mass, and women have more fat mass than men. Men are more likely to accumulate adipose tissue around the trunk and abdomen, whereas women usually accumulate adipose tissue around the hips and thighs. Less is known about sex differences in ectopic fat depots. Advances in imaging allow the noninvasive assessment of abdominal and femorogluteal fat compartments, intramyocellular lipids, intrahepatic lipids, pericardial adipose tissue, and neck adipose tissue including brown adipose tissue and tongue adipose tissue. In this review, sex differences of regional adipose tissue, muscle mass, ectopic lipids, and brown adipose tissue and their effects on cardiometabolic risk will be discussed. In addition, novel imaging techniques to quantify these body composition compartments noninvasively will be described.

Changes in whole-body fat distribution, intrahepatic lipids, and insulin resistance of obese adolescents during a low-level lifestyle intervention.

The aim of this study was to analyze changes in adipose tissue (AT) distribution, intrahepatic lipids (IHL), and insulin resistance (IR) among a group of obese adolescents undergoing a 7-months low-level lifestyle intervention. Thirty-nine obese Caucasian adolescents (mean age 13.9 years, body mass index standard deviation score (BMI-SDSLMS) 2.14) were included. AT and IHL were determined by T1-weighted magnetic resonance (MR) imaging and single-voxel MR spectroscopy; IR was estimated using the homeostatic model assessment (HOMA-IR). The lifestyle intervention led to a reduction of both BMI-SDSLMS (boys 2.27 to 2.17; girls 2.00 to 1.82) and HOMA-IR (boys 6.1 to 4.4 (p = 0.008); girls 6.2 to 4.7 (p = 0.030)). IHL dropped in both genders (boys 7.5 to 4.3 %; girls 4.6 to 3.4 %) positively correlating with HOMA-IR (boys r = 0.52; girls r = 0.68), while in contrast visceral AT did not change significantly. CONCLUSIONS: Although the lifestyle intervention only slightly reduced BMI-SDSLMS, insulin sensitivity improved in both genders and came along with a marked reduction of IHL. This suggests that IHL might play the dominant role regarding insulin resistance in the youth, especially if compared to other AT compartments such as visceral AT. WHAT IS KNOWN: • MR imaging/spectroscopy can be used to evaluate body fat distribution and intrahepatic lipids in the youth. • The strength of associations between body fat compartments and insulin resistance is under scientific debate. WHAT IS NEW: • The study emphasizes that even a low-level lifestyle intervention has a beneficial effect. • The study suggests that intrahepatic lipids are an important factor in the development of insulin resistance.

Impact of peripheral thyroid hormone balance on liver fat: insights from the NutriAct trial.

OBJECTIVE: Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat. DESIGN: 502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG). METHODS: Serum levels of thyroid hormones (THs) as well as IHLs, defined via magnetic resonance spectroscopy, were measured within an euthyroid subgroup without significant alcohol consumption at baseline (n = 332) and after 12 months (n = 243). A ratio of T3/T4 was used to assess whole-body deiodinase activity. Estimates of glucose and lipid metabolism were analyzed. RESULTS: Only fT3 and T3/T4 ratios showed a significant positive correlation with IHL at baseline. We observed a significant decline in fT3, T3, fT3/fT4 ratio, and T3/T4 ratio in CG and IG after 12 months without significant differences between groups. TSH, fT4, and T4 remained stable. A larger improvement of IHL during dietary intervention was seen in those subjects with a lower decline in T3 concentrations. CONCLUSIONS: Altered TH balance indicates a possible compensatory upregulation of whole-body TH activity in subjects with increased liver fat. This might be also relevant during the improvement of hepatic steatosis.

Methodological advancements in organ-specific ectopic lipid quantitative characterization: Effects of high fat diet on muscle and liver intracellular lipids.

OBJECTIVE: Ectopic lipid accumulation is a hallmark of metabolic diseases, linking obesity to non-alcoholic fatty liver disease, insulin resistance and diabetes. The use of zebrafish as a model of obesity and diabetes is raising due to the conserved properties of fat metabolism between humans and zebrafish, the homologous genes regulating lipid uptake and transport, the implementation of the '3R's principle and their cost-effectiveness. To date, a method allowing the conservation of lipid droplets (LDs) and organs in zebrafish larvae to image ectopic lipids is not available. Our objectives were to develop a novel methodology to quantitatively evaluate organ-specific LDs, in skeletal muscle and liver, in response to a nutritional perturbation. METHODS: We developed a novel embedding and cryosectioning protocol allowing the conservation of LDs and organs in zebrafish larvae. To establish the quantitative measures, we used a three-arm parallel nutritional intervention design. Zebrafish larvae were fed a control diet containing 14% of nutritional fat or two high fat diets (HFDs) containing 25 and 36% of dietary fats. In muscle and liver, LDs were characterized using immunofluorescence confocal microscopy. In liver, intrahepatocellular lipids were discriminated from intrasinusoid lipids. To complete liver characteristics, fibrosis was identified with Masson's Trichrome staining. Finally, to confirm the conservation and effect of HFD, molecular players of fat metabolism were evaluated by RT-qPCR. RESULTS: The cryosections obtained after setting up the embedding and cryopreservation method were of high quality, preserving tissue morphology and allowing the visualization of ectopic lipids. Both HFDs were obesogenic, without modifying larvae survival or development. Neutral lipid content increased with time and augmented dietary fat. Intramuscular LD volume density increased and was explained by an increase in LDs size but not in numbers. Intrahepatocellular LD volume density increased and was explained by an increased number of LDs, not by their increased size. Sinusoid area and lipid content were both increased. Hepatic fibrosis appeared with both HFDs. We observed alterations in the expression of genes associated with LD coating proteins, LD dynamics, lipogenesis, lipolysis and fatty acid oxidation. CONCLUSIONS: In this study, we propose a reproducible and fast method to image zebrafish larvae without losing LD quality and organ morphology. We demonstrate the impact of HFD on LD characteristics in liver and skeletal muscle accompanied by alterations of key players of fat metabolism. Our observations confirm the evolutionarily conserved mechanisms in lipid metabolism and reveal organ specific adaptations. The methodological advancements proposed in this work open the doors to study organelle adaptations in obesity and diabetes related research such as lipotoxicity, organelle contacts and specific lipid depositions.

Mediterranean diet affects the metabolic outcome of metabolic dysfunction-associated fatty liver disease.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is on the rise globally. It is currently one of the most prevalent liver diseases and one of the world's important public health problems. At present, there is no consensus on a pharmacological treatment for MAFLD. By contrast, lifestyle interventions based on exercise and a balanced diet are considered to be the cornerstone of MAFLD management. Mediterranean diet (MD) have a large content of polyphenols, polyunsaturated fatty acids, oleic acid, carotenoids and fiber, which carry out antioxidant, anti-inflammatory and antibacterial benefits. It has been considered to reduce the incidence rate of cardiovascular disease and type 2 diabetes. The purpose of this narrative review is therefore to summarize and analyze the evidence for the effect of MD on metabolic outcomes in MAFLD patients.

Osteoporosis and Hepatic Steatosis: 2 Closely Related Complications in Short-Bowel Syndrome.

BACKGROUND: Osteoporosis has scarcely been prospectively investigated in short-bowel syndrome (SBS). This prospective study was designed to evaluate incretins, adipokines, bone mass, and lipid deposits from marrow adipose tissue (MAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver (IHLs). METHODS: The study comprised 2 groups matched by gender, height, and age: the control group (CG) (9 males, 9 females) and the SBS group (SBSG) (6 males, 5 females). The SBSG was evaluated twice in an interval of 1 year (SBSG0 and SBSG1 ). The biochemical evaluation included incretins, leptin, and adiponectin. Dual-energy x-ray absorptiometry and magnetic resonance were, respectively, used to measure BMD and lipid deposits. RESULTS: Bone mineral density (BMD) was lower in the SBSG than in the CG, but there was no difference between SBSG0 and SBSG1 . There was no difference in MAT, SAT, and VAT, but IHL was lower in CG than in SBSG0 and SBSG1 . A negative correlation between MAT and third lumbar vertebrae BMD was found in the CG but not in SBSG0 or SBSG1 . There was a negative association between IHL and bone mass considering all participants (CG and SBSG0 ) (R2 = 0.38; P < .05). CONCLUSION: Appropriate nutrition assistance recovers body composition, reverts the relationship of bone mass and MAT, and mitigates bone loss in SBS. In spite of this, osteoporosis seems to be an early and persistent complication in SBS. Curiously, SBS seems to be a highly vulnerable condition for the development of hepatic steatosis and shows an association between bone mass and IHL.

Acute Endothelial Benefits of Fat Restriction over Carbohydrate Restriction in Type 2 Diabetes Mellitus: Beyond Carbs and Fats.

BACKGROUND: Cardiovascular diseases (CVD) are the major cause of mortality in type 2 diabetes patients (T2DM). The causes are embedded in a complex interplay between excess body fat, insulin resistance and serum lipid anomalies. Endothelial homeostasis is strongly affected by this pathogenic network. Even though metabolic changes and weight loss improve vascular endothelial function, the effect of different dietary approaches is still uncertain for type 2 diabetes patients. OBJECTIVE: We aimed to compare the acute effects of a hypocaloric very low carbohydrate (VLC) diet versus a hypocaloric low fat (LF) diet on flow mediated dilation (FMD), intrahepatic lipid (IHL) accumulation and visceral adipose tissue as independent risk factors of CVD in T2DM patients. DESIGN: 36 T2DM patients (age 63 ± 8 years, 60% females) were randomly assigned to the VLC diet (4⁻10% of total energy intake (E)) or to the LF diet (<30% E) for 3 weeks. Endothelial function was assessed by the flow mediated dilation (FMD) method. Adipose tissue depots and IHL were determined by magnetic resonance. RESULTS: Both dietary strategies reduced body weight, body fat content and IHL. Unexpectedly, the LF group experienced significantly greater enhancement of FMD, compared to the VLC group. The FMD showed a positive correlation with protein intake and fat intake in the LF group, while it revealed a negative correlation with protein intake in the VLC diet group. CONCLUSIONS: Reduction of total and hepatic adiposity was shown to be successful using either the VLC or LF hypocaloric diets, however, improvements in FMD may be related to the interplay of fat and protein intake.