Frequently, health insurance providers reject coverage for newly developed medications targeting medlinkobesity/medlink and medlinktype 2 diabetes/medlink

New research has found a link between high-speed internet activities and Australia's growing rate of obesity.

The economic impact of obesity will reach $87.7 billion and affect one-third of Australians by 2025 based on current trends and without further intervention.

Young adults, who grew up in stable families with quality parental relationships, more likely to have healthy diet, activity and sleep behaviours, and less likely to be obese.

While the injectable forms of semaglutide have taken the world by storm, the oral form, available in India, is helping doctors see results in diabetes control, with the added benefit of weight loss, even though the cost remains a deterrent

It’s not just your waistline that suffers as you put on weight. Researchers are beginning to find puzzling new links between obesity, memory loss and dementia

Lucy Cheke and her colleagues at the University of Cambridge recently invited a few participants into her lab for a kind of ‘treasure hunt’.

The participants navigated a virtual environment on a computer screen, dropping off various objects along their way. They then answered a series of questions to test their memory of the task, such as where they had hidden a particular object.

Related: How your eyes betray your thoughts

Related: How to optimise your brain's waste disposal system

Related: Gut bacteria regulate nerve fibre insulation

Related: Obesity linked to memory deficits

Later this year the Court of Justice of the EU (CJEU) is expected to give a ruling addressing, for the first time, the extent to which EU law protects workers against discrimination on grounds of obesity.  In the meantime, one of the CJEU&rsquo...

Advocate General (AG) Jääskinen has concluded that there is no general principle of EU law prohibiting discrimination in the labour market, and that includes discrimination on grounds of obesity as a self-standing ground of unlawful discri...

Around one in five adults in France are obese. While this is below the OECD average, obesity still has a significant impact. The French live on average 2.3 years less due to overweight. Overweight accounts for 4.9% of health expenditure; and lowers labour market outputs by the equivalent of 671 thousand full time workers per year. Combined, this means that overweight reduces France’s GDP by 2.7%.

While the prevalence of obesity in Italy is lower than in most other countries, it still has significant consequences. Italians live on average 2.7 years less due to overweight. Overweight accounts for 9.0% of health expenditure, above the average for other countries. Labour market outputs are lower due to overweight by the equivalent of 571 thousand full time workers per year.

Just under one in four adults in Germany are obese. As a result, Germans live on average 2.6 years less due to overweight. Overweight accounts for 10.7% of health expenditure one of the largest rates of all countries analysed. Labour market outputs are lower due to overweight by the equivalent of 1 m full time workers per year. Combined, this means that overweight reduces Germany’s GDP by 3.0%.

Dietary capsaicin elicits proteomic shifts in rats fed a high-fat diet.

A new study of marmosets, small South American monkeys, indicates that obesity may begin very early in life and suggests that marmosets may be a helpful model for obesity in humans.

The post Is obesity predestined at infancy? Marmoset study may help scientists find out. appeared first on Smithsonian Insider.

Americas progress in arresting its obesity epidemic has been too slow, and the condition continues to erode productivity and cause millions to suffer from potentially debilitating and deadly chronic illnesses.

A new UK study suggests that there are associations between obesity, physical activity, and levels of CO2 emissions from transport. These associations seem mostly to reflect the fact that obese people tend to travel longer distances by motorised forms of travel. They may also partly reflect less ‘active travel’ by bicycle or walking by obese people.

Traffic pollution contributes to childhood obesity, a recent study concludes. In the US investigation of over 4 500 children, the researchers estimated that air pollution increased the body mass index (BMI) of 10-year olds in the most polluted areas of study by 0.4 units, compared to those in the least polluted areas. It is thought that pollution may have slowed the children’s metabolism.

“Inconvenient Truth” producer Laurie David teams up with Katie Couric to make a film that has the Grocery Manufacturers Association defending its efforts.

These half-dozen exercises will help you shed pounds if obesity is in your genes.

Researchers warn health care providers that obesity is not the only factor that can contribute to Type 2 diabetes.

If your car isn't getting the gas mileage you want or expect, it might be time to put down the carbs and pick up the dumbbells because your body may be the prob

Mayor announced a plan to offer his employees discounts to Weight Watchers.

I used to interview elite bodybuilders on their training and eating for a living and did this for years and years. One reoccurring theme that kept popping up when talk turned to diet/nutrition was how much food top bodybuilders packed away on a daily basis.

Christopher Carroll, MD, discusses an article published in Pediatric Critical Care Medicine titled, "Childhood Obesity Increases Duration Of Therapy During Severe Asthma Exacerbations." Dr. Carroll is a pediatric intensivist at Connecticut Children's Medical Center. (Pediatr Crit Care Med. 2006:527-31)

Research Highlights: Teens who have obesity, type 2 diabetes or high systolic blood pressure show greater signs of blood vessel aging compared to healthy, normal weight teens. Thicker and stiffer blood vessels were more likely among teens that had...

Method and apparatus for limiting absorption of food products in specific parts of the digestive system is presented. A gastrointestinal implant device is anchored in the pyloric portion of the gastrointestinal system and extends beyond the ligament of Treitz. All food exiting the stomach is funneled through the device. The gastrointestinal device includes an anchor for anchoring the device in the pyloric portion and a flexible sleeve that extents into the duodenum. The anchor is collapsible for endoscopic delivery and removal.

Systems and methods for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and treating hyperglycemia, Alzheimer's disease, sleep disorders, Parkinson's disease, Attention Deficit Disorder and nicotine addiction involve synchronizing and tailoring the administration of nutraceuticals, medications and other substances in accordance with the body's natural circadian rhythms, meal times and other factors. Improved control of blood glucose levels, extended alertness, and weight control, and counteracting of disease symptoms when they are at their worst are possible. An automated, pre-programmable transdermal administration system is used to provide pulsed doses of medications, pharmaceuticals, hormones, neuropeptides, anorexigens, pro-drugs, stimulants, nutraceuticals, phytochemicals, phytonutrients, enzymes, antioxidants, essential oils, fatty acids, minerals, vitamins, amino acids, coenzymes, or other physiological active ingredient or precursor. The system can utilize a pump, pressurized reservoir, a system for removing depleted carrier solution, or other modulated dispensing actuator, in conjunction with porous membranes or micro-fabricated structures.

To mark the occasion of Anti Obesity Day on November 26, the company would provide DNA scan to individuals at its centres countrywide and also educate them on issues leading to the problem such as weight gain, exercise and food habits etc.

A new government study has concluded that obesity causes about 112,000 deaths each year in the United States, far fewer than a previous, highly publicized estimate by another part of the same agency.

Figures from the Australian Bureau of Statistics show almost 78 per cent of Katherine residents are now either overweight or obese, the highest proportion in the country. But the town's Mayor is not quite convinced.

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.

Once a problem only in the developed world, obesity is now a worldwide epidemic. The overwhelming cause of the epidemic is a dramatic increase in the food supply and in food consumption not a surprise. Yet there are still many mysteries about weight change that can.t be answered either inside the lab, because of the impracticality of keeping people isolated for long periods of time, or outside, because of the unreliability of dietary diaries. Mathematical models based on differential equations can help overcome this roadblock and allow detailed analysis of the relationship between food intake, metabolism, and weight change. The models. predictions fit existing data and explain such things as why it is hard to keep weight off and why obese people are more susceptible to further weight gain. Researchers are also investigating why dieters often plateau after a few months and slowly regain weight. A possible explanation is that metabolism slows to match the drop in food consumed, but models representing food intake and energy expenditure as a dynamical system show that such a weight plateau doesn.t take effect until much later. The likely culprit is a combination of slower metabolism and a lack of adherence to the diet. Most people are in approximate steady state, so that long-term changes are necessary to gain or lose weight. The good news is that each (enduring) drop of 10 calories a day translates into one pound of weight loss over three years, with about half the loss occurring in the first year. For More Information: Quantification of the effect of energy imbalance on bodyweight, Hall et al. Lancet, Vol. 378 (2011), pp. 826-837.

Priscilla Hollander
Jul 1, 2007; 20:159-165
Articles

Taewook Kang
Apr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882
Research

The onset of obesity-linked type 2 diabetes (T2D) is marked by an eventual failure in pancreatic β-cell function and mass that is no longer able to compensate for the inherent insulin resistance and increased metabolic load intrinsic to obesity. However, in a commonly used model of T2D, the db/db mouse, β-cells have an inbuilt adaptive flexibility enabling them to effectively adjust insulin production rates relative to the metabolic demand. Pancreatic β-cells from these animals have markedly reduced intracellular insulin stores, yet high rates of (pro)insulin secretion, together with a substantial increase in proinsulin biosynthesis highlighted by expanded rough endoplasmic reticulum and Golgi apparatus. However, when the metabolic overload and/or hyperglycemia is normalized, β-cells from db/db mice quickly restore their insulin stores and normalize secretory function. This demonstrates the β-cell’s adaptive flexibility and indicates that therapeutic approaches applied to encourage β-cell rest are capable of restoring endogenous β-cell function. However, mechanisms that regulate β-cell adaptive flexibility are essentially unknown. To gain deeper mechanistic insight into the molecular events underlying β-cell adaptive flexibility in db/db β-cells, we conducted a combined proteomic and post-translational modification specific proteomic (PTMomics) approach on islets from db/db mice and wild-type controls (WT) with or without prior exposure to normal glucose levels. We identified differential modifications of proteins involved in redox homeostasis, protein refolding, K48-linked deubiquitination, mRNA/protein export, focal adhesion, ERK1/2 signaling, and renin-angiotensin-aldosterone signaling, as well as sialyltransferase activity, associated with β-cell adaptive flexibility. These proteins are all related to proinsulin biosynthesis and processing, maturation of insulin secretory granules, and vesicular trafficking—core pathways involved in the adaptation of insulin production to meet metabolic demand. Collectively, this study outlines a novel and comprehensive global PTMome signaling map that highlights important molecular mechanisms related to the adaptive flexibility of β-cell function, providing improved insight into disease pathogenesis of T2D.

To ensure fetal lipid supply, maternal blood triglyceride (TG) concentrations are robustly elevated during pregnancy. Interestingly, a lower increase in maternal blood TG concentrations has been observed in some obese mothers. We have shown that high-fat (HF) feeding during pregnancy significantly reduces maternal blood TG levels. Therefore, we performed this study to investigate if and how obesity alters maternal blood TG levels. Maternal obesity was established by prepregnant HF feeding (ppHF), which avoided the dietary effect during pregnancy. We found that maternal blood TG concentrations in ppHF dams were not only remarkably lower than control dams, but the TG peak occurred earlier during gestation. Hepatic TG production and intestinal TG absorption were unchanged in ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased blood TG clearance contributes to the decreased blood TG concentrations in ppHF dams. Although significantly higher levels of UCP1 protein were observed in iBAT of ppHF dams, Ucp1 gene deletion did not restore blood TG concentrations in ppHF dams. Expression of the angiopoietin-like protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregnancy. However, the pregnancy-induced elevation of blood TG was almost abolished in Angptl4^-/- dams. Compared with control dams, Angptl4 mRNA levels were significantly lower in iBAT, gWAT and livers of ppHF dams. Importantly, ectopic overexpression of ANGPTL4 restored maternal blood TG concentrations in ppHF dams. Together, these results indicate that ANGPTL4 plays a vital role in increasing maternal blood TG concentrations during pregnancy. Obesity impairs the rise of maternal blood TG concentrations by reducing ANGPTL4 expression in mice.

Branched chain amino acids (BCAAs) are associated with the progression of obesity-related metabolic disorders, including T2DM and non-alcoholic fatty liver disease. However, whether BCAAs disrupt the homeostasis of hepatic glucose and lipid metabolism remains unknown. In this study, we observed that BCAAs supplementation significantly reduced high-fat (HF) diet-induced hepatic lipid accumulation while increasing the plasma lipid levels and promoting muscular and renal lipid accumulation. Further studies demonstrated that BCAAs supplementation significantly increased hepatic gluconeogenesis and suppressed hepatic lipogenesis in HF diet-induced obese (DIO) mice. These phenotypes resulted from severe attenuation of Akt2 signaling via mTORC1- and mTORC2-dependent pathways. BCAAs/branched-chain α-keto acids (BCKAs) chronically suppressed Akt2 activation through mTORC1 and mTORC2 signaling and promoted Akt2 ubiquitin-proteasome-dependent degradation through the mTORC2 pathway. Moreover, the E3 ligase Mul1 played an essential role in BCAAs/BCKAs-mTORC2-induced Akt2 ubiquitin-dependent degradation. We also demonstrated that BCAAs inhibited hepatic lipogenesis by blocking Akt2/SREBP1/INSIG2a signaling and increased hepatic glycogenesis by regulating Akt2/Foxo1 signaling. Collectively, these data demonstrate that in DIO mice, BCAAs supplementation resulted in serious hepatic metabolic disorder and severe liver insulin resistance: insulin failed to not only suppress gluconeogenesis but also activate lipogenesis. Intervening BCAA metabolism is a potential therapeutic target for severe insulin-resistant disease.

Sodium glucose co-transporter-2 inhibitors (SGLT2i) have favorable cardiovascular outcomes in diabetic patients. However, whether SGLT2i can improve obesity-related cardiac dysfunction is unknown. Sestrin2 is a novel stress-inducible protein that regulates AMPK-mTOR and suppresses oxidative damage. The aim of this study was to determine whether empagliflozin (EMPA) improves obesity-related cardiac dysfunction via regulating Sestrin2-mediated pathways in diet-induced obesity. C57BL/6J mice and Sestrin2 knockout mice were fed a high-fat diet (HFD) for 12 weeks and then treated with or without EMPA (10 mg/kg) for 8 weeks. Treating HFD-fed C57BL/6J mice with EMPA reduced body weight, whole-body fat, and improved metabolic disorders. Furthermore, EMPA improved myocardial hypertrophy/fibrosis and cardiac function, and reduced cardiac fat accumulation and mitochondria injury. Additionally, EMPA significantly augmented Sestrin2 levels, increased AMPK and eNOS phosphorylation, but inhibited Akt and mTOR phosphorylation. These beneficial effects were partially attenuated in HFD-fed Sestrin2 knockout mice. Intriguingly, EMPA treatment enhanced the Nrf2/HO-1-mediated oxidative stress response, suggesting antioxidant and anti-inflammatory activity. Thus, EMPA improved obesity-related cardiac dysfunction via regulating Sestrin2-mediated AMPK-mTOR signaling and maintaining redox homeostasis. These findings provide a novel mechanism for the cardiovascular protection of SGLT2i in obesity.

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.

Obesity is a risk factor for type 2 diabetes (T2D), however not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from T2D and non-T2D (ND) especially obese donors (BMI ≥30 kg/m²). Islets from obese T2D donors had reduced insulin secretion, decreased β-cell exocytosis and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis and reduced granule docking. This was accompanied with reduced expression of the exocytotic proteins, SNAP25, STXBP1 and VAMP2, likely because CD36 induced down-regulation of the IRS proteins, suppressed insulin signaling PI3K-AKT pathway and increased nuclear localization of the transcription factor FoxO1. CD36 antibody treatment of the human β-cell line, EndoC-βH1, increased IRS1 and exocytotic protein levels, improved granule docking and enhanced insulin secretion. Our results demonstrate that β-cells from obese T2D donors have dysfunctional exocytosis likely due to an abnormal lipid handling represented by differential CD36 expression. Hence, CD36 could be a key molecule to limit β-cell function in T2D associated with obesity.

Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance.

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.

Andrew S. Kimball
Sep 1, 2017; 66:2459-2471
Immunology and Transplantation

Richard J. Johnson
Oct 1, 2013; 62:3307-3315
Perspectives in Diabetes

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

Patrice D. Cani
Jul 1, 2007; 56:1761-1772
Obesity Studies