Keep up with your weight loss goals with daily weighing

According to research presented in the American Heart Association’s 2018 scientific meeting, daily weighing may help with weight loss goals. People who don’t weigh themselves at all or rarely were less likely to lose weight than those who weighed themselves often,

Researchers examined the self-weighing patterns of 1,042 adults (78 percent male, 90 percent white, average age 47) and whether there were differences in weight change by these self-weighing patterns over 12 months. They analyzed remotely transmitted self-weighing data from Health eHeart, an ongoing prospective e-cohort study. The participants weighed themselves at home as they normally would, without interventions, guidance or weight-loss incentives from researchers.

Researchers identified several categories of self-weighing adults, from those that weighed themselves daily or almost daily to adults who never used at-home scales.

They found that people who never weighed themselves or only weighed once a week did not lose weight in the following year. Those that weighed themselves six to seven times a week had a significant weight loss (1.7 percent) in 12 months.

Citation: Daily weighing may be key to losing weight
American Heart Association Meeting  Poster Presentation Sa2394 – Session: NR.APS.01
Yaguang Zheng, Ph.D., M.S.N., R.N., University of Pittsburgh School of Nursing, Pittsburgh, PA

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Aspartame in sweeteners promotes weight gain in an animal study

A team of Massachusetts General Hospital (MGH) investigators has found a possible mechanism explaining why the use of the sugar substitute aspartame might not promote weight loss. In their report published online in Applied Physiology, Nutrition and Metabolism, the researchers show how the aspartame breakdown product phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome a group of symptoms associated with type 2 diabetes and cardiovascular disease. They also showed that mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets lacking aspartame.

Aspartame molecular structure. Credit: Ben Mills, Wikipedia.

“Sugar substitutes like aspartame are designed to promote weight loss and decrease the incidence of metabolic syndrome, but a number of clinical and epidemiologic studies have suggested that these products don’t work very well and may actually make things worse,” says Richard Hodin, MD, of the MGH Department of Surgery, the study’s senior author. “We found that aspartame blocks a gut enzyme called intestinal alkaline phosphatase (IAP) that we previously showed can prevent obesity, diabetes and metabolic syndrome; so we think that aspartame might not work because, even as it is substituting for sugar, it blocks the beneficial aspects of IAP.”

In a 2013 study published in Proceedings of the National Academy of Sciences, Hodin’s team found that feeding IAP to mice kept on a high-fat diet could prevent the development of metabolic syndrome and reduce symptoms in animals that already had the condition. Phenylalanine is known to inhibit the action of IAP, and the fact that phenylalanine is produced when aspartame is digested led the researchers to investigate whether its inhibitory properties could explain aspartame’s lack of a weight-loss effect.

In a series of experiments the team first found that the activity of IAP was reduced when the enzyme was added to a solution containing an aspartame-sweetened soft drink but remained unchanged if added to a solution with a sugar-sweetened beverage. IAP is primarily produced in the small intestine, and the researchers found that injecting an aspartame solution into segments of the small intestines of mice significantly reduced the enzyme’s activity. In contrast, IAP activity remained unchanged in bowel segments injected with a saline solution.

To better represent the effects of consuming beverages or other products containing aspartame, the researchers followed four groups of mice for 18 weeks. Two groups were fed a normal diet, one receiving drinking water with aspartame, the other receiving plain water. The other two groups were fed a high-fat diet, along with either aspartame-infused or plain water. Animals in the normal diet group that received aspartame consumed an amount equivalent to an adult human’s drinking about three and a half cans of diet soda daily, and aspartame-receiving animals in the high-fat group consumed the equivalent of almost two cans.

At the end of the study period, while there was little difference between the weights of the two groups fed a normal diet, mice on a high-fat diet that received aspartame gained more weight than did those on the same diet that received plain water. Aspartame-receiving mice in both diet groups had higher blood sugar levels than did those fed the same diets without aspartame, which indicates glucose intolerance, and both aspartame-receiving groups had higher levels of the inflammatory protein TNF-alpha in their blood, which suggests the kind of systemic inflammation associated with metabolic syndrome.

“People do not really understand why these artificial sweeteners don’t work. There has been some evidence that they actually can make you more hungry and may be associated with increased calorie consumption. Our findings regarding aspartame’s inhibition of IAP may help explain why the use of aspartame is counterproductive,” says Hodin, who is a professor of Surgery at Harvard Medical School. “While we can’t rule out other contributing mechanisms, our experiments clearly show that aspartame blocks IAP activity, independent of other effects.”

Citation: Gul, Sarah Shireen, A. Rebecca L. Hamilton, Alexander R. Munoz, Tanit Phupitakphol, Liu Wei, Sanjiv K. Hyoju, Konstantinos P. Economopoulos, Sara Morrison, Dong Hu, Weifeng Zhang, Mohammad Hadi Gharedaghi, Haizhong Huo, Sulaiman R. Hamarneh and Richard A. Hodin. “Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.” Applied Physiology, Nutrition, and Metabolism 2016pp:1-7
DOI: 10.1139/apnm-2016-0346 
Adapted from press release by Massachusetts General Hospital.

Research shows red cabbage microgreens reduce weight gain and lower cholesterol in mice fed on high-fat diet

Microgreens are sprouting up everywhere from upscale restaurants to home gardens. They help spruce up old recipes with intense flavors and colors and are packed with nutrients. Now research has shown that for mice on a high-fat diet, red cabbage microgreens helped lower their risk factors for developing cardiovascular disease and reduce their weight gain. The report appears in ACS’ Journal of Agricultural and Food Chemistry.

In an animal study, red cabbage microgreens helped lower “bad” cholesterol. Credit: American Chemical Society

Microgreens are tender, immature plants and herbs that take only a week or two to grow before they’re ready for harvesting. A growing body of research suggests that microgreens could offer more health benefits than their mature counterparts. And since previous studies have shown that full-grown red cabbage can help guard against excessive cholesterol, Thomas T.Y. Wang and colleagues wanted to see if red cabbage microgreens might have a similar or even greater effect than their larger counterparts.

To test their hypothesis, the researchers used mice that were a modelled for obesity. These animals also tend to develop high cholesterol and other risk factors for cardiovascular disease. The team divided 60 of these mice into different diet groups. They received food low in fat or high in fat, and with or without either red cabbage microgreens or mature red cabbage. Both the microgreens and mature cabbage diets reduced weight gain and levels of liver cholesterol in the mice on high-fat diets. The study showed that microgreens intake lowered LDL cholesterol, liver triglyceride, and inflammatory cytokine levels in the animals. 

Citation: Huang, Haiqiu, Xiaojing Jiang, Zhenlei Xiao, Lu Yu, Quynhchi Pham, Jianghao Sun, Pei Chen, Wallace Yokoyama, Liangli Lucy Yu, Yaguang Sunny Luo, and Thomas T. Y. Wang. “Red cabbage microgreen lower circulating LDL, liver cholesterol and inflammatory cytokines in mice fed a high fat diet.” Journal of Agricultural and Food Chemistry (2016).
DOI: 10.1021/acs.jafc.6b03805
Research funding: U.S. Department of Agriculture.
Adapted from press release by The American Chemical Society.

New approach to treating Obesity with fat burning molecule ABX300

A small molecule ABX300 could provide valuable help in combating the global epidemic of obesity. When it was fed to obese mice, the animals’ metabolism sped up and their excess weight was shed. It is doing so by recruiting the help of a body’s own genes in countering the effects of a high-fat diet. The research team conducting the study believes their findings may provide a new unexplored therapeutic approach to fighting excessive weight gain in cases where diets or exercise have no effect. The study was led by Julien Santo, Celia Lopez-Herrera and Cécile Apolit of a French biotechnology company, and is published in Springer Nature’s International Journal of Obesity.

A high-fat diet may contribute to obesity in some individuals. Treatment in such situations has focused on behavioral changes, which is highly challenging to achieve for the general population on a long term basis. This study introduces the concept of recruiting the help of our genes in countering the effects of a high-fat diet, instead of focusing on reducing the intake of high-fat food.
Researchers know that the structure of some genes that help to produce certain proteins can actually change when someone constantly eats too much high-fat food. In the process, the person can become overweight or obese, or develop other lifestyle-related metabolic disorders such as diabetes or heart problems. In many cases, the same gene can produce two or more alternate proteins, based on how the translation from DNA (gene) to proteins is processed. One of these genes is LMNA, which plays a role in the development of different metabolic disorders. The LMNA RNA, which is the genetic material resulting from a process called DNA transcription, is modified by three SR proteins called SRSFI, SRSF5, and SRSF6. In this process called splicing, the genetic material encoded in the RNA is basically diced or shifted around and therefore alters the resulting proteins.

The research team found that a small molecule ABX300 is able to change the way one particular SR protein, SRSFI, works in the bodies of mice that gained excessive weight after being fed a high-fat diet. SRSFI determines which of the gene products of opposing effects could be produced from a single LMNA gene. One gene product promotes fat storage, the other opposes it. This study showed that blocking SRSFI with a compound promotes gene expression of the protein that burns calories and prevents fat gain or induces fat loss when mice are on a high-fat diet. It did not have any effect on lean mice of normal weight.

According to the research team, this approach alters the animals’ metabolic rate or energy expenditure. It means that it can speed up the metabolism of obese animals and that their bodies start to function at a higher energy level shedding the excess weight. In the process, their bodies started to burn much more fat, as especially fatty acids serve as much-needed sources of energy.

“The results of this animal study show that this molecule can abrogate or do away with the effect of a high-fat diet,” says Santo.

“Dietary management and exercise are not always successful as an intervention for obesity, underscoring the need for efficient medication to treat metabolic disorders,” adds Lopez-Herrera, who believes that this treatment represents an as yet unexplored approach to treating obesity.

According to Apolit, this compound did not seem to have any adverse effects, so more research in animals and eventual research in humans is needed. If the studies are positive, this may be a new way to treat obesity.

Citation: Santo J, Lopez-Herrera C, Apolit C, Bareche Y, Lapasset L, et. al. “Pharmacological modulation of LMNA SRSF1-dependent splicing abrogates diet-induced obesity in mice”. International Journal of Obesity 2016.
DOI: 10.1038/ijo.2016.220
Adapted from press release by Springer.

Understanding signaling pathway that creates brown fat to help in fight against obesity and diabetes

A signaling pathway in fat cells may one day provide the key to better treatments for obesity, according to new research by scientists at the Perelman School of Medicine at the University of Pennsylvania. They reported their findings in Genes & Development.

This image shows adipose tissue, with fat droplets in green
and blood vessels in red. Credit: The laboratory of
Zoltan Arany, MD, PhD, Perelman School of Medicine,
 University of Pennsylvania
Ordinary fat cells, also called white adipocytes, stuff themselves with fat molecules to store up energy, and their overloading leads to obesity and related conditions, including diabetes. Brown adipocytes, which are prevalent in children as “baby fat,” but much less so in adults, do virtually the opposite: they burn energy rapidly to generate heat and thereby protect the body from cold as well as obesity and diabetes. The signaling pathway discovered by the Penn scientists activates a “browning program” in white adipocytes, making them more like energy-burning brown adipocytes.
“It’s conceivable that one would be able to target this pathway with a drug, to push white fat to become brown fat and thereby treat obesity,” said the study’s senior author Zoltan P. Arany, MD, Ph.D., an associate professor of Cardiovascular Medicine. About 36 percent of American adults are considered obese and nearly 10 percent have type 2 diabetes.

Arany and colleagues found that the browning program in white adipocytes is normally suppressed by a protein called FLCN. It performs this function in cooperation with a major cellular signaling hub, a protein complex known as mTOR. The FLCN-mTOR interaction keeps the browning program switched off by preventing a protein called TFE3 from entering the cell nucleus.

The scientists showed that deleting the FLCN gene in the white adipocytes of mice allows TFE3 to migrate into the nucleus, where it binds to DNA and activates a key regulator of cellular metabolism called PGC-1β. It then turns on the set of genes for the browning program.

In the mice in which FLCN was deleted, white adipocytes became visibly browner as they produced more mitochondria–tiny, oxygen reactors that supply chemical energy within cells and convert energy to heat in brown adipocytes. In several other ways too, including their altered cellular structures, mitochondria’s higher capacity for consuming oxygen, and their distinctive pattern of gene expression, the cells became more like brown adipocytes.

Arany and his team showed that they could reproduce this browning effect merely by forcing the overexpression of PGC-1β in the white adipocytes of mice. “In principle, a drug that boosts the activity of PGC-1β or some of its target genes might serve as a therapeutic activator of the browning program to curb obesity and treat or prevent diabetes,” Arany said.

Aside from its potential medical relevance, the discovery is an important advance in understanding cell biology. “Cellular metabolism is regulated by major signaling pathways and with this study, we’re linking two of these major pathways, the mTOR, and the PGC-1 pathways,” Arany said. “The connection between them hasn’t been well understood, but here we’re clarifying it significantly.”

Arany and his team plan further studies of the pathway and its relation to other mTOR signaling pathways.

Citation:“The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue”. Shogo Wada, Michael Neinast, Cholsoon Jang, Yasir H. Ibrahim, Gina Lee, Apoorva Babu, Jian Li, Atsushi Hoshino, Glenn C. Rowe, James Rhee, José A. Martina, Rosa Puertollano, John Blenis, Michael Morley, Joseph A. Baur, Patrick Seale and Zoltan Arany. Genes & development 2016.
DOI: 10.1101/gad.287953.116
Research funding: National Institutes of Health.
Adapted from press release by Perelman School of Medicine at the University of Pennsylvania.

Research discovers beneficial role of omega-3 fatty acids on brown fat

Omega-3 fatty acids are able to stimulate the activation of brown and beige adipose tissues, a discovery that would promote the development of new therapies for obesity and other metabolism diseases, according to a research study published in the journal Nature Communications under the supervision of Professor Francesc Villarroya, from the Department of Biochemistry and Molecular Biomedicine and the Biomedical Research Center Red-Fisiopatología de la Obesidad y Nutrición (CIBEROBN) of the Institute of Health Carlos III.

In the new study, carried out in laboratory animal models, the research team noticed that Omega-3 fatty acids (n-3 PUFAS) stimulate the activation of brown and beige adipose tissue through a specific receptor (GPR120), which enables the release of the hormone FGF21 (21 fibroblast growth factor). This hormone, built by the adipocyte, is a molecule that regulates lipid glucose and metabolism and therefore, it is an effective target for the action mechanism of Omega-3.

“This discovery has implications in the understanding of the positive effects of n-3 PUFAS on the control of metabolic diseases and other aspects regarding the treatment for obesity and type 2 diabetes”, says Professor Francesc Villarroya, member of the Institute of Biomedicine of the University of Barcelona (IBUB) and head of the Research Group in Genetics and Molecular Biology of Mitochondrial Proteins and Associated Diseases.

The study shows that Omega-3 fatty acids enable the adaptive thermogenesis in mammals’ brown adipose tissue, an essential mechanism for the adaptation of the organism to cold environments. With rodents, it has been proved that the brown adipose tissue is able to create warmth and protect from obesity through the activation of energy expenditure.

The main function of brown adipose tissue is to burn calories and to make physical warmth out of fat (thermogenesis). However, a recent study by this research team has defined that brown adipose tissue also acts as an endocrine organ and can secrete factors that activate fat and carbohydrates metabolism. The most known factors up to now are FGF21, neuregulin 4 and interleukin-6, among other molecules of biological interest.

According to Francesc Villarroya, “these molecules, released by the adipose tissue (brown adipocytes or batokines) have positive metabolic effects. For this reason, they could be used in new therapies for obesity and related metabolic diseases”.

Citation: “The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes” Tania Quesada-López, Rubén Cereijo, Jean-Valery Turatsinze, Anna Planavila, Montserrat Cairó, Aleix Gavaldà-Navarro, Marion Peyrou, Ricardo Moure, Roser Iglesias, Marta Giralt, Decio L. Eizirik & Francesc Villarroya. Nature Communications 2016 vol: 7 pp: 13479
DOI: http://dx.doi.org/10.1038/ncomms13479
Adapted from press release by Universitat de Barcelona

Obese patients with monoclonal gammopathy of undetermined significance (MGUS) are at higher risk of progression to multiple myeloma

New research shows that excess weight increases the risk that a benign blood disorder will progress into multiple myeloma, a cancer of the blood. The study, by a team at Washington University School of Medicine in St. Louis, is published Nov. 18 in the Journal of the National Cancer Institute.

Being overweight or obese has been known to increase the risk of multiple myeloma, a cancer of the plasma cells in the blood and bone marrow that develops more often after age 60. Multiple myeloma is preceded by a blood disorder called monoclonal gammopathy of undetermined significance (MGUS) in which abnormal plasma cells produce many copies of an antibody protein. This precancerous condition does not cause symptoms and often goes undiagnosed.

“But our findings show that obesity can now be defined as a risk factor for developing multiple myeloma through this condition,” said the study’s first author, Su-Hsin Chang, Ph.D., an assistant professor of surgery in the Division of Public Health Sciences at Washington University. “For patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS), maintaining a healthy weight may be a way to prevent the progression to multiple myeloma, if further confirmed by clinical trials.”

The researchers analyzed data from a U.S. Department of Veterans Affairs database, identifying 7,878 patients, predominately men, diagnosed with monoclonal gammopathy of undetermined significance (MGUS) from October 1999 through December 2009.

Among these patients, 39.8 percent were overweight and 33.8 percent were obese. The researchers then tracked whether the patients developed multiple myeloma. They found that 4.6 percent of overweight patients (followed for a median of 5.75 years) and 4.3 percent of obese patients (followed for a median of 5.9 years) developed multiple myeloma, compared with 3.5 percent of people at normal weight (followed for a median of 5.2 years) – a difference that is statistically significant.

Overweight and obese monoclonal gammopathy of undetermined significance (MGUS) patients had a 55 percent and 98 percent higher risk of progression to multiple myeloma, respectively, than normal-weight MGUS patients.

African-American men also were more likely than their Caucasian counterparts to experience a progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.

Monoclonal gammopathy of undetermined significance (MGUS) is caused by elevated levels of an antibody protein, known as M protein, that is found in 3 percent of people over age 50. By itself, MGUS is difficult to diagnose and often does not warrant treatment. “The diagnosis is usually by accident, often driven by tests performed for the diagnosis or management of other conditions,” Chang said. “Although our study does not directly suggest screening for MGUS, regular check-ups can help physicians monitor whether MGUS is progressing to other disorders, including multiple myeloma.”

Multiple myeloma is the third most common type of blood cancer. An estimated 30,330 new cases of multiple myeloma will be diagnosed in 2016, and 12,650 deaths will be attributed to the disease, according to the American Cancer Society.

“Based on our finding that being overweight or obese is a risk factor for multiple myeloma in MGUS patients, and since extra weight is a modifiable risk factor, we hope that our results will encourage intervention strategies to prevent the progression of this condition to multiple myeloma as soon as MGUS is diagnosed,” Chang said. “Also, for black people diagnosed with MGUS, close monitoring of the disease progression, in addition to maintaining a healthy weight, should be prioritized.”

Future studies are planned by Chang and other School of Medicine researchers – including senior author Kenneth R. Carson, MD, PhD, an assistant professor of oncology, and Graham Colditz, MD, DrPH, a cancer expert who also is associate director of prevention and control at Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. “In the future, we will look at whether healthy weight loss is inversely associated with the progression of multiple myeloma in MGUS patients or how weight change plays a role in the progression of MGUS to multiple myeloma,” Chang said.

Citation: Chang SH, Luo S, Thomas TS, O’Brian KK, Colditz GA, Carlsson NP, Carson KR. Obesity and the Transformation of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma: A Population-Based Cohort Study. Journal of the National Cancer Institute. Nov. 18, 2016.
DOI:
Research funding: Foundation for Barnes-Jewish Hospital, Siteman Cancer Center, National Institutes of Health, Agency for Healthcare Research and Quality, American Cancer Society.
Adapted from press release by Washington University School of Medicine in St. Louis.

Research shows Weight loss can lead to strong increase in appetite

Analysis of a trial that used the drug canagliflozin found that as people lost weight, their appetite increased proportionately, leading to consumption of more calories and weight loss plateau (leveling off). The findings provide the first measurement in people of how strongly appetite counters weight loss as part of the body’s feedback control system regulating weight. Results are currently available on BioRxiv and will publish in Obesity.

A team led by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) analyzed data from a year-long, placebo-controlled, double-blind trial in people with type 2 diabetes who could eat and drink without restriction by the study. Of the 242 participants, 153 received canagliflozin, a drug that caused a substantial increase in the amount of glucose excreted in their urine. Those people were not directly aware of that calorie loss, which caused a gradual decrease in weight averaging about eight pounds.

The team used a validated math model to calculate the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people who got a placebo. However, for every pound of lost weight, the people treated with canagliflozin consumed about 50 calories per day more than they were eating before the study. This increase in appetite and calorie intake led to slowing of weight loss after about six months.

The measurements are consistent with the researchers’ analysis of data from a separate trial on a commercial weight loss program not involving canagliflozin. In the weight loss program trial, despite the dieters’ consistent efforts to reduce calorie intake, their increased appetite resulted in a progressive increase in calorie intake — three times stronger than the changes in caloric expenditure that typically accompany weight loss — and weight loss plateau. Findings from the analyses suggest that persistent effort is required to avoid weight regain.

Publication: How strongly does appetite counter weight loss? Quantification of the homeostatic control of human energy intake.
DOI: http://dx.doi.org/10.1101/051045
Journal:

Adapted from press release by National Institute of Health.