Likewise, an accompanying study led by Steven Kliewer of the University of Texas Southwestern Medical Center found that FGF21 mobilizes fat in food-restricted animals and those with chronically elevated concentrations of the liver hormone.
'We think these findings would increase the desirability of a drug that [might work through this mechanism] to increase fat oxidation in the liver,' said Maratos-Flier, noting that the rise in obesity has contributed to a growing epidemic of nonalcoholic fatty liver disease.
Mammals survive periods of nutrient deprivation by shifting from carbohydrates to so-called ketone bodies as a primary fuel source.
Ketone bodies are produced from fatty acids transferred from storage in fat tissue to the liver when carbohydrates are scarce. During prolonged fasts, ketone bodies can provide nearly half of baseline energy requirements and up to 70% of the energy required by the brain.
Maratos-Flier's team examined changes in gene activity occurring in mice fed a high-fat, low-carb diet for 30 days. Their comprehensive genetic screen of the animals, which lost weight on the special diet, turned up FGF21.'We saw a dramatic increase in FGF21 in the livers of the mice [on the diet],' she said.
Kliewer's group showed that FGF21 is induced directly by PPAR (peroxisome proliferator-activated receptor) in liver in response to fasting in mice. Scientists have known that PPAR controls fats' use as an energy source during starvation. In addition, some drugs that lower 'bad' cholesterol work by targeting PPAR. FGF21 in turn stimulates lipid breakdown in white adipose tissue and ketone body production in the liver. They unexpectedly also found that FGF21 led the animals to reduce their physical activity and made them more sensitive to entering torpor, a short-term, hibernation-like state.
'During fasting, the liver hormone communicates with adipose tissue to send fat to the liver. It turns on the metabolism of fat into ketone bodies—and at the same time, it sensitizes the animals to going into torpor to conserve energy. It's clear that FGF21 is a principal component of the fasting.' she added.
Source: Eurekalert
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