To which I say
She really had to think to come up with that one.
The Connection Between Oxygen and Diabetes
A lack of O2 in fat cells triggers inflammation and insulin resistance in obesity
Researchers at the University of California, San Diego School of Medicine have, for the first time, described the sequence of early cellular responses to a high-fat diet, one that can result in obesity-induced insulin resistance and diabetes. The findings, published in the June 5 issue of Cell, also suggest potential molecular targets for preventing or reversing the process.
“We’ve described the etiology of obesity-related diabetes. We’ve pinpointed the steps, the way the whole thing happens,” said Jerrold M. Olefsky, MD, associate dean for Scientific Affairs and Distinguished Professor of Medicine at UC San Diego. “The research is in mice, but the evidence suggests that the processes are comparable in humans and these findings are important to not just understanding how diabetes begins, but how better to treat and prevent it.”
More than 25 million Americans have diabetes – 8.3 percent of the population – with another 79 million Americans estimated to be pre-diabetic, according to the American Diabetes Association. Diabetes is characterized by high blood sugar levels poorly regulated by either inadequate insulin production or because cells to not respond properly to the regulating hormone. Diabetes is the seventh leading cause of death in the United States and a major risk factor for other life-threatening conditions, including heart disease and stroke.
Past research by Olefsky and others has shown that obesity is characterized by low-grade inflammation in adipose or fat tissues and that this inflammatory state can become chronic and result in systemic insulin resistance and diabetes. In today’s Cell paper, the scientists describe the earliest stages of the process, which begins even before obesity becomes manifest.
First authorYun Sok Lee, PhD, a project scientist in Olefsky’s lab, and colleagues fed mice a high-fat diet. They observed that the abundant saturated fatty acids in the diet activated adenine nucleotide translocase 2 (ANT2), a mitochondrial protein in fat cell membranes that is involved in cellular energy metabolism.
Activation of ANT2 caused increased oxygen consumption, which meant less was available for the rest of the cell. The result was a relative state of hypoxia or inadequate oxygen supply, one that subsequently induced production of a protective transcription factor in fat cells called HIF-1alpha. In turn, HIF-1alpha triggered release of chemokines, proteins that signal cellular distress, launching the immune system’s inflammatory response. A sustained high-fat diet ensured that the process continued unabated, leading to obesity, chronic low-grade tissue inflammation and eventually, insulin resistance in the mice.
The elucidation of this sequence also revealed two potential therapeutic targets: ANT2 and HIF-1alpha. The researchers suggest that inhibiting either could blunt, or even reverse, the damaging cellular sequence. Indeed, they found that mice genetically engineered to lack HIF-1alpha in their adipocytes were protected from high-fat diet-induced inflammation, insulin resistance and elevated glucose levels.
Pictured: Colorized scanning electron micrograph of adipocytes or fat cells. Image courtesy of Steve Gschmeissner.
A kindergarten student is sent to the school nurse because she has been vigorously scratching her scalp for a few hours. The nurse’s first action will be to assess the child for the presence of which of the following?
Researchers at the University of California, San Diego School of Medicine have mapped the transmission network of human immunodeficiency virus (HIV) in San Diego. The mapping of HIV infections, which used genetic sequencing, allowed researchers to predictively model the likelihood of new HIV transmissions and identify persons at greatest risk for transmitting the virus.
The findings are published online in the June 5 issue of the journal PLOS ONE.
“The more we understand the structure and dynamics of an HIV transmission network, the better we can identify ‘hot spots’ of transmission,” said Susan Little, MD, professor of medicine at the UC San Diego AntiViral Research Center and lead author of the study.
“Not everyone who is HIV-infected is equally likely to transmit the infection to others. There are clusters of more active disease transmission. We can use this information to target treatment interventions to those most likely to transmit the virus to others and markedly reduce the number of new infections.”
The researchers analyzed the HIV-1 sequence data from recently HIV-1 infected persons and their sexual and social contacts in San Diego, between 1996 and 2011. Sequence data were collected as part of routine HIV genetic testing used to determine if a virus is resistant to certain classes of HIV medications. Genetic similarities between viral sequences infecting different people were compared. Viruses from two people with a high degree of genetic similarity were suggestive of a transmission link. The scientists noted that viral similarity does not independently prove that a transmission occurred, only that the individuals are part of a closely connected transmission network.
Within the observed HIV transmission network, researchers calculated a transmission network score (TNS) to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner. Participants with a high TNS were significantly more likely than those with low TNS to develop a close linkage to another person within their first year of HIV infection, suggestive of onward transmission.
Through network modeling, investigators showed that using this information to deploy antiretroviral therapy (ART) to individuals with the highest TNS resulted in a significantly greater likelihood of reduced new HIV-1 transmissions than providing ART to the same number of randomly selected individuals.
“Focusing our prevention and treatment resources to the populations at greatest risk of transmission could dramatically reduce the number of new infections associated with these populations,” said Little. “Used in conjunction with traditional partner services, TNS-guided treatment and prevention interventions could markedly lower rates of new HIV infection in our community.”
Pictured: HIV particles on a cell. Thomas Deerinck, UCSD NCMIR
Osteoporosis (Brittle Bone Disease)
Sure, everyone has most likely heard about Osteoporosis and many of us will probably have to deal with it at some time in our later lives. These color enhanced SEMs, showing the actions of human osteoclast cells on the surface of our bones, provide a visual picture of just how this occurs. Notice how the surface of the bone appears to have been “chewed away” by the osteoclasts.
Osteoclasts are large, multi-nucleated cells that form from the fusion of several macrophage cells within our bones. Osteoclasts move about by extending their cellular processes. They are normally present in our bodies to absorb and remove unwanted bone tissue during normal bone regeneration or in response to growth or changing mechanical stress on the skeleton. This process is known as resorption.
The underlying mechanism of osteoporosis is the disparity between bone resorption (by osteoclasts) and bone formation (by osteoblasts). An imbalance of certain body chemicals can result in an increase in the activation of osteoclasts. This in turn leads to excessive bone loss. Osteoporosis itself has no symptoms. Its main consequence is the increased risk of bone fractures. These fractures occur in situations where healthy people would not normally break a bone. They are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, rib, hip and wrist.
Above images © Eye of Science / Science Source
Under the microscope.