Leptin is a hormone made by fat cells which regulates the amount of fat stored in the body. Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. However, this homeostatic system can be overridden by the activation of 'emergency response circuits' that mediate feeding responses to emergent or stressful stimuli. Inhibition of these circuits is therefore permissive for normal energy homeostasis to occur, and their chronic activation can cause profound, even life-threatening, changes in body fat mass, says new research, "Neurobiology of food intake in health and disease," published online May 20, 2014 in Nature Reviews Neuroscience. And more research reviews on leptin appear online in a June 1, 2014 issue of Nature Reviews Neuroscience.
The neurobiology of food intake review explains how under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. However, this homeostatic system can be overridden by the activation of 'emergency response circuits' that mediate feeding responses to emergent or stressful stimuli.
Inhibition of these circuits is therefore permissive for normal energy homeostasis to occur, and their chronic activation can cause profound, even life-threatening, changes in body fat mass. This Review highlights how the interplay between homeostatic and emergency feeding circuits influences the biologically defended level of body weight under physiological and pathophysiological conditions. You also may wish to check out the 'Review.'
Another noteworthy news of a recent research finding is "Mother's high-fat diet alters metabolism in offspring, leading to higher obesity risk." The offspring of obese mothers consuming a high-fat diet during pregnancy are at a higher risk than the children of thin mothers for lifelong obesity and related metabolic disorders. The molecular and cellular basis for these differences are clarified in a new study published in the Jan. 23, 2014 issue of Cell by researchers at Yale University School of Medicine and the University of Cologne.
Conducted in mice, the study showed that the offspring of mothers who consumed a high-fat diet during lactation had abnormal neuronal circuits in the hypothalamus — a key brain region that regulates metabolism. Our study suggests that expecting mothers can have major impact on the long-term metabolic health of their children by properly controlling nutrition during this critical developmental period of the offspring," said the study's co-lead author Tamas Horvath, according to the January 23, 2014 Yale University news release, "Mother's high-fat diet alters metabolism in offspring, leading to higher obesity risk." Horvath is the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine.
Horvath and his collaborators at the Max Planck Institute for Neurological Research and at the University of Cologne developed a mouse model of metabolic programming. They found that mouse mothers fed a high-fat diet during breastfeeding had offspring with abnormal neuronal connections in the hypothalamus, as well as altered insulin signaling in this brain circuit. As a result, the offspring remained overweight and had abnormalities in glucose metabolism throughout life.
Horvath and his colleagues said the study helps identify the key point in pregnancy when maternal nutrition has the most impact on an offspring's metabolic health, according to the news release
Because of developmental differences between species — neural circuits in the hypothalamus continue to develop after birth in mice, but are fully developed before birth in humans — the findings suggest that the third trimester of pregnancy in humans is the most critical period. That's when a mother's diet will most likely have long-lasting effects on her offspring's health, according to the researchers.
"Mothers can control or even reverse their offspring’s predisposition to obesity and resulting diseases by altering their food intake," said Horvath. "Because gestational diabetes frequently manifests during the third trimester, the results could inform more intense screening of mothers for alterations in glucose metabolism."
Other authors on the study include Merly C. Vogt, Lars Paeger, Simon Hess, Sophie M. Steculorum, Motoharu Awazawa, Brigitte Hampel, Susanne Neupert, Hayley T. Nicholls, Jan Mauer, A. Christine Hausen, Reinhard Predel, Peter Kloppenburg, Tamas L. Horvath, and Jens C. Brüning.
The study was funded in part by the National Institutes of Health NIH (DP1 DK006850, R01AG040236, and P01NS062686), the American Diabetes Association, the Helmholtz Society (ICEMED), and The Klarman Foundation.
Now, comes the question of leptin
There's another noteworthy paper, "Extra brain cells curb appetite," from back in 2005, and then there's the article, "Leptin fights depression." But now, new research shows that leptin also influences brain cells that control appetite, Yale researchers find. Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of cells to control appetite. Published in the June 1, 2014 issue of Nature Neuroscience, the findings could lead to development of treatments for metabolic disorders such as obesity and diabetes. You may wish to check out an abstract of the findings in Nature Neuroscience doi: 10.1038/nn.3725, published online June 1, 2014. Or see, the SuppVersity website posting for news about this research.
"Up until now, the scientific community thought that leptin acts exclusively in neurons to modulate behavior and body weight," said senior author Tamas L. Horvath, according to the June 1, 2014 Yale news release, "Leptin also influences brain cells that control appetite, Yale researchers find." Horvath is the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine. "This work is now changing that paradigm."
Leptin, a naturally occurring hormone, is known for its hunger-blocking effect on the hypothalamus, a region in the brain. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.
Leptin's effect on metabolism has been found to control the brain's neuronal circuits, but no previous studies have definitively found that leptin could control the behavior of cells other than neurons
To test the theory, Horvath and his team selectively knocked out leptin receptors in the adult non-neuronal glial cells of mice. The team then recorded the water and food intake, as well as physical activity every five days. They found that animals responded less to feeding reducing effects of leptin but had heightened feeding responses to the hunger hormone ghrelin.
"Glial cells provide the main barrier between the periphery and the brain," said Horvath, according to the news release. "Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes."
Other authors on the study include Jae Geun Kim, Shigetomo Suyama, Marco Koch, Sungho Jin, Pilar Argente-Arizon, Jesus Argente, Zhong-Wu Liu, Marcelo R Zimmer, Jin Kwon Jeong, Klara Szigeti-Buck, Yuanqing Gao, Cristina Garcia-Caceres, Chun-Xia Yi, Natalina Salmaso, Flora M Vaccarino, Julie Chowen, Sabrina Diano, Marcelo O. Dietrich, and Matthias H. Tschöp.