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New anti obesity drug on the way

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A new drug which destroys blood supply to fatty tissue could help people lose a tenth of their body weight in just one month, a study indicates.

Obese rhesus monkeys lost on average 11 per cent of their body weight after four weeks of the experimental treatment.

Body mass index (BMI) and waistline also were reduced, while all three measures were unchanged in untreated control monkeys.

Imaging studies also showed a substantial decrease in body fat among treated animals.

A research team led by scientists at The University of Texas MD Anderson Cancer Centre carried out the study.

Co-senior author Professor Renata Pasqualini, at the David H. Koch Centre for Applied Research of Genitourinary Cancers, said: “Development of this compound for human use would provide a non-surgical way to actually reduce accumulated white fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat.”

She said previous attempts to treat obesity have predominantly focused on drugs aimed at suppressing appetite or increasing metabolism, but these efforts have been hampered by their toxic side-effects.

The MD Anderson group designed a new drug, which includes a homing agent that binds to a protein on the surface of fat-supporting blood vessels and a synthetic peptide that triggers cell death.

Their blood supply gone, fat cells are reabsorbed and metabolised.

Co-senior author Professor Wadih Arap, said: “Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible.”

In earlier preclinical research, obese mice lost about 30 per cent of their body weight with the drug, now called Adipotide.

The drug acts on white adipose tissue, the scientific name for the unhealthy type of fat that accumulates under the skin and around the abdomen, and is a disease and mortality predictor.

Prof Pasqualini said: “Most drugs against obesity fail in transition between rodents and primates.

Obesity

Obesity

“We’re greatly encouraged to see substantial weight loss in a primate model of obesity that closely matches the human condition.”

The primate model also shares other physiological features associated with human obesity, such as metabolic syndrome, characterised by an increased resistance to insulin, which can lead to the development of type 2 diabetes and cardiovascular disease.

Adipotide-treated monkeys showed marked improvements in insulin resistance – using about 50 per cent less insulin after treatment.

Now the research team are preparing for a clinical trial in which obese prostate cancer patients would receive daily injections of Adipotide for 28 consecutive days.

Prof Arap said: “The question is, will their prostate cancer become better if we can reduce their body weight and the associated health risks?”

He said some prostate cancer treatments, such as hormone therapy, cause weight gain.

Greater weight can lead to arthritis, which in turn causes inactivity that leads to more weight gain.

Fat cells also secrete growth hormones that cancer cells thrive on.


Weight, BMI and abdominal circumference all continued to drop for three weeks after treatment ended before turning back up during the eighth week of the study.

Treated monkeys’ abdominal fat levels fell by 27 per cent during the study. Fat levels increased slightly in the control group.

Lean monkeys did not lose weight in a separate study to test for potential effects of the drug in non-obese animals, indicating that the drug’s effect may be selective for obese subjects.

Monkeys in the studies remained bright and alert throughout, interacting with caretakers and demonstrating no signs of nausea or food avoidance.

This is potentially an important finding since unpleasant side-effects have limited the use of approved drugs that reduce fat absorption in the intestines.

The principal side effects were noted in the kidneys.

Study first author Dr Kirstin Barnhart, a veterinary clinical pathologist said: “The renal effect was dose-dependent, predictable and reversible.”

The results were published in the journal Science Translational Medicine.

Coffee protects against type 2 diabetes

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Coffee, that morning elixir, may give us an early jump-start to the day, but numerous studies have shown that it also may be protective against type 2 diabetes. Yet no one has really understood why.

Now, researchers at UCLA have discovered a possible molecular mechanism behind coffee’s protective effect. A protein called sex hormone-binding globulin (SHBG) regulates the biological activity of the body’s sex hormones, testosterone and estrogen, which have long been thought to play a role in the development of type 2 diabetes. And coffee consumption, it turns out, increases plasma levels of SHBG.

Reporting with colleagues in the current edition of the journal Diabetes, first author Atsushi Goto, a UCLA doctoral student in epidemiology, and Dr. Simin Liu, a professor of epidemiology and medicine with joint appointments at the UCLA School of Public Health and the David Geffen School of Medicine at UCLA, show that women who drink at least four cups of coffee a day are less than half as likely to develop diabetes as non-coffee drinkers.

When the findings were adjusted for levels of SHBG, the researchers said, that protective effect disappeared.

Cup of coffee

Cup of coffee

The American Diabetes Association estimates that nearly 24 million children and adults in the U.S. — nearly 8 percent of the population — have diabetes. Type 2 diabetes is the most common form of the disease and accounts for about 90 to 95 percent of these cases.

Early studies have consistently shown that an “inverse association” exists between coffee consumption and risk for type 2 diabetes, Liu said. That is, the greater the consumption of coffee, the lesser the risk of diabetes. It was thought that coffee may improve the body’s tolerance to glucose by increasing metabolism or improving its tolerance to insulin.

“But exactly how is elusive,” said Liu, “although we now know that this protein, SHBG, is critical as an early target for assessing the risk and prevention of the onset of diabetes.”


Earlier work by Liu and his colleagues published in the New England Journal of Medicine had identified two mutations in the gene coding for SHBG and their effect on the risk of developing type 2 diabetes; one increases risk while the other decreases it, depending on the levels of SHBG in the blood.

A large body of clinical studies has implicated the important role of sex hormones in the development of type 2 diabetes, and it’s known that SHBG not only regulates the sex hormones that are biologically active but may also bind to receptors in a variety of cells, directly mediating the signaling of sex hormones.

“That genetic evidence significantly advanced the field,” said Goto, “because it indicated that SHBG may indeed play a causal role in affecting risk for type 2 diabetes.”

“It seems that SHBG in the blood does reflect a genetic susceptibility to developing type 2 diabetes,” Liu said. “But we now further show that this protein can be influenced by dietary factors such as coffee intake in affecting diabetes risk — the lower the levels of SHBG, the greater the risk beyond any known diabetes risk factors.”

For the study, the researchers identified 359 new diabetes cases matched by age and race with 359 apparently healthy controls selected from among nearly 40,000 women enrolled in the Women’s Health Study, a large-scale cardiovascular trial originally designed to evaluate the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer.

Cup of coffee

Cup of coffee

They found that women who drank four cups of caffeinated coffee each day had significantly higher levels of SHBG than did non-drinkers and were 56 percent less likely to develop diabetes than were non-drinkers. And those who also carried the protective copy of the SHBG gene appeared to benefit the most from coffee consumption.

When the investigators controlled for blood SHBG levels, the decrease in risk associated with coffee consumption was not significant. This suggests that it is SHBG that mediates the decrease in risk of developing type 2 diabetes, Liu said.

And there’s bad news for decaf lovers. “Consumption of decaffeinated coffee was not significantly associated with SHBG levels, nor diabetes risk,” Goto said. “So you probably have to go for the octane!”

Other authors of the study included Brian Chen, of UCLA, and Julie Buring, JoAnn Manson and Yiqing Song, of Brigham and Women’s Hospital and Harvard Medical School. Funding was provided by the National Institutes of Health. No conflicts of interest were reported by the authors.