We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells’ inflammatory phenotype may impact obesity and its complications.

To predict how diet shapes a person’s gut microbiome, researchers came up with a new way to categorize foods.

Dieter Ruehle, the organist for the Dodgers and Kings, is having a tough time living through the sports famine, but he has a secret coping mechanism.

HOW to live longer: If you are looking to lead a long life, eating a healthy, balanced diet is the hard and fast rule to live by. The best diet to follow is still debated vigorously but there is a broad consensus emerging.

ANXIETY and other common mental health problems normally plague around one in six adults and are more common in women than men. So how do you stop anxiety in its tracks?

MELANIA TRUMP is the only First Lady to be a former lingerie model, and is certainly one of the most glamorous. But how does she keep her figure so trim now that she's in the White House?

THE SIRTFOOD diet is a weight loss plan that has attracted celebrity fans in recent years. The trendy diet is said to be the secret behind Adele's dramatic weight loss. But what are sirtfoods and what can you eat on the plan?

WEIGHT LOSS can often be a daunting thought for some but with this easy diet plan it can help burn fat while boosting energy levels. What is the diet?

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

Gretchen Benson
Feb 1, 2011; 24:36-40
Nutrition FYI

Caroline Trapp
Feb 1, 2012; 25:38-44
Nutrition FYI

Teri L. Hernandez
May 1, 2016; 29:82-88
From Research to Practice

Sandi M. Azab
Mar 31, 2020; 0:jlr.D120000630v1-jlr.D120000630
Methods

Inês Magro dos Reis
Apr 14, 2020; 0:jlr.RA120000632v1-jlr.RA120000632
Research Articles

Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first  identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (-3) FA correlated with self-reported total -3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from  total FA serum hydrolysates. In the intervention cohort, serum -3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 x 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires.

Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1^nih), creating a dysfunctional NPC1 protein. Npc1^nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1^nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1^nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the non-oxidative branch of the PPP which connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically delete TKT in mouse adipocytes and find no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuates high fat diet (HFD)-induced obesity, reduces hepatic steatosis, improves glucose tolerance, alleviates insulin resistance and increases energy expenditure. Mechanistically, TKT deficiency accumulates non-oxidative PPP metabolites, decreases glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity, but also suggest limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n=5-8/group) and juvenile offspring (n=8/group). In vivo signaling was evaluated after an insulin bolus just prior to weaning (n=4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action suggesting earlier interventions may be warranted.

Maria Sörhede Winzell
Dec 1, 2004; 53:S215-S219
Section V: The Incretin Pathway

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

Mary C. Gannon
Sep 1, 2004; 53:2375-2382
Pathophysiology

Fruit Plant Original Pelangsing Badan Herbal terbuat dari Sayuran Dan Buah-Buahan Berkualitas Tinggi Mampu Menjadikan Sehat Serta Langsing Secara Cepat

Obat Pelangsing Badan Herbal Fatloss Jimpness Beauty Penghilang Lemak Seketika Merupakan Obat Pelangsing Badan Yang Aman Dikonsumsi Untuk Pria Maupun Wanita

Pelangsing Badan Herbal Lida Daidaihua Adalah Pelangsing Badan Yang Mengandung Bahan Herbal Yang Sangat Cepat Menurunkan Berat Badan, Aman Dan Cepat .

Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcr^m–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcr^m–/m– mice than in control Hmgcr^fl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcr^m–/m– and Hmgcr^fl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity.

They have a big impact on the diet of American citizens, and those of most Western nations, so why does the expert advice underpinning US government dietary guidelines not take account of all the relevant scientific evidence asks Nina Teicholz. Read the full investigation: http://www.bmj.com/content/351/bmj.h4962

Richard S Surwit
Sep 1, 1988; 37:1163-1167
Original Article

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

Upon the passing of his physical on Tuesday, the Reds signed infielder/outfielder Derek Dietrich to a Minor League contract with an invitation to big league camp for Spring Training.

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

Type 2 diabetes accounts for 90% of the population with diabetes, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. The aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of the population with type 2 diabetes and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed a 45% kcal as fat diet for 8 weeks before administering streptozotocin, 30 mg/kg body weight (T2D), and compared with age- and duration-matched type 1 diabetic rats (T1D) (60 mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared with age-matched T1D rats. While at 4 months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and Rac1 promoter DNA methylation was exacerbated. At 6 months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good lifestyle and BMI could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in patients with diabetes.

Jennifer B. Marks
Oct 1, 2004; 22:155-156
Editorials

OBJECTIVE

Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle.

OBJECTIVE

To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post–myocardial infarction (MI) patients.

OBJECTIVE

Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population.

John P Bantle
Sep 1, 1993; 16:1301-1305
Short Report

Peter J Garlick
Dec 1, 1991; 14:1189-1198
Diet and Diabetes

Anastassios G. Pittas
Dec 1, 2005; 28:2939-2941
BR Clinical Care/Education/Nutrition

Thomas M S Wolever
Apr 1, 1992; 15:562-564
Short Report

George A. Bray
Apr 1, 2014; 37:950-956
Current Concepts of Type 2 Diabetes Prevention

Frank B. Hu
Jun 1, 2011; 34:1249-1257
Kelly West Award Lecture