To this end, a research team at the Gladstone Institute of Cardiovascular Disease, led by Suneil Koliwad, MD, PhD, recently added new details that link obesity to diabetes and heart disease.
When individuals become obese from overeating, cells called adipocytes located in the fat tissue fill up with dietary fats and begin to die. Immune cells called macrophages move out of the blood stream and into this tissue, where they accumulate around dying adipocytes. As the macrophages work to clear away the dead cells, they are exposed to large amounts of dietary fat that can result in unwanted consequences. Exposure to saturated fats, in particular, causes the macrophages to enter an inflammatory state. In this state, the macrophages secrete cytokines, such as tumor necrosis factor (TNF) alpha, that encourage the development of insulin resistance, diabetes, and heart disease.
The Gladstone team hypothesized that enhancing the capacity of macrophages to store dietary fats might alter this process. To do this, they focused on an enzyme called DGAT1, which makes triglycerides from dietary fats for storage as cellular energy reserves.
They examined a transgenic strain of mice (aP2-Dgat1) that make large amounts of DGAT1 in both adipocytes and macrophages. On a high-fat diet, these mice became obese, but the macrophages in their fat tissue did not undergo inflammatory activation, and the mice were protected from developing systemic inflammation, insulin resistance, and fatty livers, all problems that were profound in the control mice.
Even more interesting was the team's finding that the protection against diet-induced inflammation and insulin resistance could be conferred on normal mice simply by replacing their macrophages with those from aP2-Dgat1 mice by bone marrow transplantation.
"We found in experimental mice that a single enzyme, DGAT1, in macrophages is involved in many of the problems associated with obesity," said Dr. Koliwad. "This is exciting because humans have this enzyme as well, providing the potential for a therapeutic target to examine."
Using cultured cells, the team also showed that increasing the amount of DGAT1 expressed by macrophages increased their capacity to store triglycerides and protected them against inflammatory activation by saturated fats. Moreover, DGAT1 expression was increased by treatment of macrophages with PPARgamma agonists, which are widely used agents to treat diabetes, and DGAT1 was required for these agents to protect macrophages against inflammatory activation induced by saturated fats.
"Our results are very exciting," said Dr. Robert Farese, senior author on the study. "We have used DGAT1 as a tool to uncover a mechanism by which macrophages might protect individuals from developing serious consequences of obesity."
Koliwad SK, Streeper RS, Monetti M, Cornelissen I, Chan L, Terayama K, Naylot S, Rao M, Hubbard B, Farese RV, Jr. Increased capacity for triacylglycerol synthesis in macrophages protects mice from deleterious consequences of diet-induced obesity. J. Clin. Invest., In press.
Robert V. Farese's primary affiliation is with the Gladstone Institute of Cardiovascular Disease, where he is senior investigator and where his laboratory is located and his research is conducted. He is also a professor of medicine, biochemistry and biophysics at the University of California, San Francisco.
About the Gladstone Institutes. The Gladstone Institutes is a nonprofit, independent research and educational institution, consisting of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. Independent in its governance, finances and research programs, Gladstone shares a close affiliation with UCSF through its faculty, who hold joint UCSF appointments.
Valerie Tucker | EurekAlert!
25.09.2018 | Medical University of South Carolina
Artificial intelligence to improve drug combination design & personalized medicine
25.09.2018 | SLAS (Society for Laboratory Automation and Screening)
Our brain is a complex network with innumerable connections between cells. Neuronal cells have long thin extensions, so-called axons, which are branched to increase the number of interactions. Researchers at the Max Planck Institute of Biochemistry (MPIB) have collaborated with researchers from Portugal and France to study cellular branching processes. They demonstrated a novel mechanism that induces branching of microtubules, an intracellular support system. The newly discovered dynamics of microtubules has a key role in neuronal development. The results were recently published in the journal Nature Cell Biology.
From the twigs of trees to railroad switches – our environment teems with rigid branched objects. These objects are so omnipresent in our lives, we barely...
The Fraunhofer FEP has been involved in developing processes and equipment for cleaning, sterilization, and surface modification for decades. The CleanHand Network for development of systems and technologies to clean surfaces, materials, and objects was established in May 2018 to bundle the expertise of many partnering organizations. As a partner in the CleanHand Network, Fraunhofer FEP will present the Network and current research topics of the Institute in the field of hygiene and cleaning at the parts2clean trade fair, October 23-25, 2018 in Stuttgart, at the booth of the Fraunhofer Cleaning Technology Alliance (Hall 5, Booth C31).
Test reports and studies on the cleanliness of European motorway rest areas, hotel beds, and outdoor pools increasingly appear in the press, especially during...
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
26.09.2018 | Trade Fair News
26.09.2018 | Life Sciences
25.09.2018 | Health and Medicine