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Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging: Cell Stem Cell

Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting.

Crosstalk among muscles and fat

After the rodents’ resistance exercise, which consisted of walking around, though, the animals’ leg muscles appeared depleted of miR-1. At the same time, the vesicles in their bloodstream now thronged with the stuff, as did nearby fat tissue. It seems, the scientists concluded, that the animals’ muscle cells somehow packed those bits of microRNA that retard hypertrophy into vesicles and posted them to neighboring fat cells, which then allowed the muscles immediately to grow.

Fat cells can sense sunlight—not getting enough increases metabolic syndrome risk

In the latest findings, the research team studied how mice respond when exposed to chilly temperatures—about 40° F. They already knew that mice, much like humans, use both a shivering response and an internal fat-burning response to heat themselves. Deeper analysis revealed that the internal heating process is compromised in the absence of the gene OPN3 and exposure specifically to a 480-nanometer wavelength of blue light. This wavelength is a natural part of sunlight but occurs only in low levels in most artificial light. When the light exposure occurs, OPN3 prompts white fat cells to release fatty acids into the bloodstream. Various types of cells can use these fatty acids as energy to fuel their activities. But brown fat literally burns the fatty acids (in a process called oxidation) to generate heat that warms up the chilly mice. When mice were bred to lack the OPN3 gene, they failed to warm up as much as other mice when placed in chilly conditions. But surprisingly, even mice that had the correct gene failed to warm up when they exposed to light that lacked the blue wavelength.

Fatty meal interrupts gut's communication with the body, but why? If that second helping of prime rib stuns your gut into silence, is that good or bad? -- ScienceDaily

These cells produce at least 15 different hormones to send signals to the rest of the body about gut movement, feelings of fullness, digestion, nutrient absorption, insulin sensitivity and energy storage. "But they fall asleep on the job for a few hours after a high-fat meal, and we don't yet know if that's good or bad," said John Rawls, an associate professor of molecular genetics and microbiology in the Duke School of Medicine. Since enteroendocrine cells are key players in digestion, the feeling of being full and subsequent feeding behavior, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more. "This is a previously unappreciated part of the postprandial (after-meal) cycle," Rawls said. "If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signaling, which could in turn contribute to the development of insulin resistance and Type 2 diabetes."

Some high-cholesterol genes differ between countries - ScienceBlog.com

They found that the results were broadly consistent across European and Asian groups, with about three quarters of genetic markers applied similarly across the different groups, but only 10% of the genetic markers for triglycerides (the most common type of fat in the body) were implicated in the same cardiovascular risk factors among people from Uganda.

What drives inflammation in type 2 diabetes? Not glucose, says new research - ScienceBlog.com

The team was surprised to find that glycolysis wasn’t driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.

Could coffee be the secret to fighting obesity? -- ScienceDaily

"From our previous work, we knew that brown fat is mainly located in the neck region, so we were able to image someone straight after they had a drink to see if the brown fat got hotter," said Professor Symonds. "The results were positive and we now need to ascertain that caffeine as one of the ingredients in the coffee is acting as the stimulus or if there's another component helping with the activation of brown fat. We are currently looking at caffeine supplements to test whether the effect is similar.

High-fat diet and age alter microflora and cause inflammation in heart failure: Experiments with mice show involvement of gut bacteria and spleen in this heart pathology -- ScienceDaily

They found that the obesity-generating diet caused a sharp increase in bacteria belonging to the genus Allobaculum, phylum Firmicutes. The obesity-generating diet also increased the proportion of neutrophils in the blood of young mice. In aged mice, a similar increase in the proportion of neutrophils was found for both old mice fed a standard diet and old mice fed the obesity-generating diet. The spleen, a secondary immune organ, is a known reservoir for leukocytes that are released after heart injury. Those splenic leukocytes move to the heart to begin tissue repair and help resolve inflammation. Halade and colleagues found that the obesity-generating diet and aging led to neutrophil swarming and an altered leukocyte profile after heart attack. They also observed splenic structural deformities in these mice and a decrease in splenic CD169-positive macrophages.

Fat cells work different 'shifts' throughout the day -- ScienceDaily

During this unique study seven participants underwent regulated sleep-wake cycles and meal times before entering the laboratory, where they maintained this routine for a further three days. Participants then experienced a 37- hour 'constant routine' during which time they did not experience daily changes in light-dark, feed-fast and sleep-wake cycles. Biopsies of fat tissue were taken at six hourly intervals and then followed by an analysis of gene expression. Researchers identified 727 genes in the fat tissue that express their own circadian rhythm, many carrying out key metabolic functions. A clear separation in gene rhythms was identified with approximately a third peaking in the morning and two thirds in the evening.

Protein released from fat after exercise improves glucose -- ScienceDaily

"In contrast to the negative effects of many adipokines, our study identified transforming growth factor beta 2 (TGF-beta 2) as an adipokine released from adipose tissue (fat) in response to exercise that actually improves glucose tolerance," says Laurie J. Goodyear, PhD, Head of Joslin's Section on Integrative Physiology and Metabolism and study co-author. Not only did exercise-stimulated TGF-beta 2 improve glucose tolerance, treating obese mice with TGF beta 2 lowered blood lipid levels and improved many other aspects of metabolism. "The fact that a single protein has such important and dramatic effects was quite impressive," says Goodyear, Professor of Medicine at Harvard Medical School. Two years ago, the international research team first demonstrated that adipose tissue offers beneficial metabolic effects in response to exercise. "Our hypothesis was that exercise is changing the fat, and as a result of that change, the fat releases these beneficial proteins into the bloodstream," says Goodyear. "Before this discovery, we always just focused on the positive effects of muscle."

Everything You Know About Obesity Is Wrong - The Huffington Post

Doctors have shorter appointments with fat patients and show less emotional rapport in the minutes they do have. Negative words—“noncompliant,” “overindulgent,” “weak willed”—pop up in their medical histories with higher frequency. In one study, researchers presented doctors with case histories of patients suffering from migraines. With everything else being equal, the doctors reported that the patients who were also classified as fat had a worse attitude and were less likely to follow their advice. And that’s when they see fat patients at all: In 2011, the Sun-Sentinel polled OB-GYNs in South Florida and discovered that 14 percent had barred all new patients weighing more than 200 pounds.

Take a Vacation From Exercise? Your Body May Not Thank You - The New York Times

Like the adults in the other study, these older volunteers quickly developed worse blood sugar control during their two weeks of barely moving. Insulin resistance climbed. Some developed changes in muscle tissue indicating that they might soon begin to lose muscle mass, and a few had to be removed from the study because they had edged into full-blown Type 2 diabetes after becoming inactive. For most of the men and women who remained in the experiment, their undesirable metabolic changes were not fully reversed after two weeks of moving about again.

A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. - PubMed - NCBI

The daily intake duration (95% interval) exceeded 14.75 hr for half of the cohort. When overweight individuals with >14 hr eating duration ate for only 10-11 hr daily for 16 weeks assisted by a data visualization (raster plot of dietary intake pattern, "feedogram") that we developed, they reduced body weight, reported being energetic, and improved sleep. Benefits persisted for a year.

Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges - ScienceDirect

Here we tested TRF in mice under diverse nutritional challenges. We show that TRF attenuated metabolic diseases arising from a variety of obesogenic diets, and that benefits were proportional to the fasting duration. Furthermore, protective effects were maintained even when TRF was temporarily interrupted by ad libitum access to food during weekends, a regimen particularly relevant to human lifestyle. Finally, TRF stabilized and reversed the progression of metabolic diseases in mice with preexisting obesity and type II diabetes. We establish clinically relevant parameters of TRF for preventing and treating obesity and metabolic disorders, including type II diabetes, hepatic steatosis, and hypercholesterolemia.

Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet - ScienceDirect

To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

Strategic fasting improves race times

In this particular study, both groups actually consumed the same amount of carbohydrates, but the sleep-low group ate all of theirs between their morning and afternoon sessions while the control group also had carbs after their second workout. Both groups completed a test triathlon to assess their fitness and then a second one three weeks later to determine the effectiveness of the training method. The sleep-low group had improved their running times on the 10-km segment by an average of 75 seconds while the control group showed no improvement. The sleep low athletes also lost about 3 pounds of body fat while the control group stayed the same.

Our muscles measure the time of day -- ScienceDaily

Biochemistry Department of the Faculty of Sciences, UNIGE, who codirected the study in Geneva with colleague Charna Dibner, from the Department of Internal Medicine Specialties, from the Faculty of Medicine, UNIGE. "As the combination of lipids varied substantially from one individual to another, we needed further evidence to corroborate these findings," he explains. In a second step, the researchers switched to an in-vitro experiment. They cultivated human muscle cells and artificially synchronised them in the absence of a master clock, using a signal molecule normally secreted in the body. The researchers observed a periodic variation in the cell's lipid composition, similar to what they noticed in human subjects. But when they disrupted the clock mechanism by inhibiting the responsible genes, the periodically changing variations in the lipids were mostly lost.

The Benefits of Exercising Before Breakfast - The New York Times

At the end, the nonexercising group was, to no one’s surprise, super-sized, having packed on an average of more than six pounds. They had also developed insulin resistance — their muscles were no longer responding well to insulin and weren’t pulling sugar (or, more technically, glucose) out of the bloodstream efficiently — and they had begun storing extra fat within and between their muscle cells. Both insulin resistance and fat-marbled muscles are metabolically unhealthy conditions that can be precursors of diabetes. The men who ate breakfast before exercising gained weight, too, although only about half as much as the control group. Like those sedentary big eaters, however, they had become more insulin-resistant and were storing a greater amount of fat in their muscles. Only the group that exercised before breakfast gained almost no weight and showed no signs of insulin resistance. They also burned the fat they were taking in more efficiently. “Our current data,” the study’s authors wrote, “indicate that exercise training in the fasted state is more effective than exercise in the carbohydrate-fed state to stimulate glucose tolerance despite a hypercaloric high-fat diet.”

The Best Thing to Eat Before a Workout? Maybe Nothing at All - The New York Times

Most obviously, the men displayed lower blood sugar levels at the start of their workouts when they had skipped breakfast than when they had eaten. As a result, they burned more fat during walks on an empty stomach than when they had eaten first. On the other hand, they burned slightly more calories, on average, during the workout after breakfast than after fasting. But it was the impacts deep within the fat cells that may have been the most consequential, the researchers found. Multiple genes behaved differently, depending on whether someone had eaten or not before walking. Many of these genes produce proteins that can improve blood sugar regulation and insulin levels throughout the body and so are associated with improved metabolic health. These genes were much more active when the men had fasted before exercise than when they had breakfasted.

Run on empty

Gene expression in the adipose tissue differed significantly in the two trials. The expression of two genes, PDK4 and HSL, increased when the men fasted and exercised and decreased when they ate before exercising. The rise in PDK4 likely indicates that stored fat was used to fuel metabolism during exercise instead of carbohydrates from the recent meal. HSL typically increases when adipose tissue uses stored energy to support increased activity, such as during exercise, explained Dylan Thompson, corresponding author of the study. These results reinforce the view that "adipose tissue often faces competing challenges," Thompson wrote. After eating, adipose tissue "is busy responding to the meal and a bout of exercise at this time will not stimulate the same [beneficial] changes in adipose tissue. This means that exercise in a fasted state might provoke more favorable changes in adipose tissue, and this could be beneficial for health in the long term," he noted.