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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development


A protein that promotes the breakdown of fat

Researchers have found a protein on the surface of fat droplets — especially in the muscles of endurance athletes — that can kick-start a more efficient breakdown of fat throughout our bodies.

These findings could have significant implications for new ways to treat obesity and type 2 diabetes, said Perry E. Bickel MD, Associate Professor of Internal Medicine at University of Texas Southwestern, USA, and senior author of the study published online in Nature Communications.

More than 29 million Americans have diabetes, the seventh leading cause of death in the USA, according to the American Diabetes Association. Almost 26 percent of those Americans being 65 and older.

The study has found a new role for the protein Perilipin 5 located in the cell nucleus. It turns out Perilipin 5 is a regulator of fat metabolism. The finding "was a complete surprise to us," said Dr. Bickel, also Chief of the Division of Endocrinology and holder of the Daniel W. Foster, M.D. Distinguished Chair in Internal Medicine.

In obese people and in rodents, excess fat can accumulate in tissues not specialized for fat storage — such as skeletal muscle, the heart, and liver. This buildup can lead to dysfunction of those tissues.

Breaking down large amounts of fat can overload a body's metabolic system, swamping tiny mitochondria in the cell as they try to turn fat into fuel. Cells can be left with partially processed fat which are toxic to mitochondria and leads to the insulin resistance seen in type 2 diabetes, Dr. Bickel adds.

Bickel: "If you overload the factory with fuel, then it does not work well."

Endurance athletes - who paradoxically accumulate at least as much fat in their muscle cells as do obese, insulin-resistant diabetics - have been found to have higher levels of Perilipin 5. The UTSW team's new findings may explain why endurance athletes can exploit the increased stored fat for grueling exercises while avoiding the toxicity of increased muscle fat.

When cultured mouse cells are stimulated to release fat stored in droplets, Perilipin 5 leaves the surface of those droplets and moves to the cell's nucleus.

In the nucleus, the fat works with the PGC-1α protein to create more efficient mitochondria.

"Perilipin 5 helps match mitochondrial capacity to burn the fat load in the cell," says Dr. Bickel.

These findings could lead to a new approach for treating obesity-related diabetes — perhaps a way to mimic Perilipin 5 or an aspect of that protein. For now, Bickel and his team continue research on the action of Perilipin 5 in mice, hoping to complete additional work by early next year.

Dysfunctional cellular lipid metabolism contributes to common chronic human diseases, including type 2 diabetes, obesity, fatty liver disease and diabetic cardiomyopathy. How cells balance lipid storage and mitochondrial oxidative capacity is poorly understood. Here we identify the lipid droplet protein Perilipin 5 as a catecholamine-triggered interaction partner of PGC-1α. We report that during catecholamine-stimulated lipolysis, Perilipin 5 is phosphorylated by protein kinase A and forms transcriptional complexes with PGC-1α and SIRT1 in the nucleus. Perilipin 5 promotes PGC-1α co-activator function by disinhibiting SIRT1 deacetylase activity. We show by gain-and-loss of function studies in cells that nuclear Perilipin 5 promotes transcription of genes that mediate mitochondrial biogenesis and oxidative function. We propose that Perilipin 5 is an important molecular link that couples the coordinated catecholamine activation of the PKA pathway and of lipid droplet lipolysis with transcriptional regulation to promote efficient fatty acid catabolism and prevent mitochondrial dysfunction.

Other contributing authors from UTSW Internal Medicine included Dr. Violeta Gallardo Montejano, lead author and Assistant Instructor; Dr. Christine Kusminski, Instructor; Dr. Chaofeng Yang, postdoctoral researcher; John McAfee, former lab technician; and Lisa Hahner, senior research scientist. Scientists from the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UT Health Science Center at Houston also participated in the study.

Some early-stage findings of the research were funded by a grant from the National Institutes of Health while Dr. Bickel worked as an endocrinologist at the UT Health Science Center at Houston.

About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 92,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.

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"Perilipin 5 helps mitochondrial burn the fat load of a cell,"
says Dr. Bickel.
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Phospholid by Wikipedia