There’s more than one type of fat cell. Besides the white fat that stores triglycerides in lipid droplets in preparation for lean times later, mammals also have heat-generating brown fat, which acts more like a radiator than a storage closet. Brown fat cells are smaller, with more abundant mitochondria than white fat cells, and they hold a lot fewer lipids. In many models of obesity, brown adipose tissue converts to white tissue, with changes in the morphology and function of the cells.
In a recent paper in the Journal of Lipid Research, Petra Kotzbeck, Antonio Giordano and colleagues investigated what happens to brown fat cells after whitening. The researchers, based at the University of Graz, Austria, and the University of Ancona, Italy, found that whitened brown adipocytes enlarged by the addition of lipids were more likely to die than white adipocytes of comparable size. Whitened adipose tissue also had more macrophages, presumably there to clean up the dead cells, and more inflammation under way. The vulnerability of whitened brown adipocytes may explain why gaining fat in the abdomen, where most whitened brown fat is located, is worse for your health than gaining subcutaneous fat.
Cells store energy in lipid droplets, and many such droplets are made in the liver, which plays an important role in coordinating fat metabolism. As new lipid droplets form within the endoplasmic reticulum, acyl coA synthetase 3, or ACSL3, is indispensable for helping them mature. ACSL3 turns free fatty acids into neutral lipids that fill the lipid droplet.
In a recent article in the Journal of Lipid Research, Hana Kimura and colleagues studying droplet synthesis at Tokyo University of Pharmacy and Life Sciences in Japan report that the binding and scaffolding protein Stx17 is required to move ACSL3 to the nascent lipid droplet at mitochondria-associated membranes within the ER. This new role may explain why Stx17 is abundantly expressed in the liver and adipocytes.
Ketogenic diets, which reduce carbohydrate intake and prompt the body to rely on fat-derived ketone bodies instead, are a popular treatment for epilepsy and thought to have neuroprotective effects on some other diseases. Mild caloric restriction is also believed to protect neurons. Researchers aren’t sure of the exact molecular mechanism of these diets, but Svenja Heischmann and colleagues at the University of Colorado in Denver have taken a step toward characterizing their effect on the brain.
In a study reported in the Journal of Lipid Research, researchers conducted a metabolomics analysis of both the plasma and brain tissue of mice eating normal or ketogenic chow. They subdivided each diet group into mice eating their fill or eating a restricted amount of chow. The researchers found that, in the bloodstream, kynurenine metabolism changed dramatically. Kynurenine, made from the amino acid tryptophan, can be converted into vitamin B3 or several other metabolites with effects on neurons. However, in the brain, the level of kynurenine changed relatively little.
The research suggests that, while tryptophan degradation is a target of the ketogenic diet, changes in plasma metabolism may not always cross the blood-brain barrier. The researchers intend to explore other metabolic changes in future publications.
Since 2013, the Journal of Lipid Research has been running a series of thematic reviews about what organizer Alfred H. Merrill Jr. originally dubbed the “Living History of Lipids.”
In his introduction to the series, Merrill described his motivation for starting the collection this way: “Much of what we know about lipids, and might be inclined to assume was easy to discover, arose from incredibly hard work, cleverly designed experiments, astonishing coincidences, and, sometimes, colossal accidents. This series of thematic reviews is intended to give glimpses into these stories. The authors will try to present the events and personalities as living histories where, when possible, readers will have a sense of stepping back in time.”
Thus far, the series has covered the lipid hypothesis of atherosclerosis, eight decades of bile acid chemistry, the discovery of essential fatty acids, what ApoE knockout and -in mice have taught us about atherogenesis, and early studies of arachidonic acid.
The latest installment, the sixth in the series, by Jean E. Vance of the University of Alberta, was published this spring. It is about the discovery, chemistry, and biochemistry of two ubiquitous phosphoglycerolipids — phosphatidylserine and phosphatidylethanolamine.
PS and PE, as they’re known for short, captured Vance’s interest back when she was a postdoctoral researcher at the University of California, San Diego, working in the lab of Daniel Steinberg. (Steinberg, by the way, wrote the first installment of the “Living History” series.).
“My interest in what I felt were the rather neglected phospholipids, PS and PE, arose from some of my preliminary data suggesting that phospholipids could be compartmentalized into distinct pools in cells, perhaps due to specific inter-organelle lipid trafficking events,” Vance recalled. “(M)y research evolved into studying the biosynthesis, cell biology and functions of PS and PE in mammalian cells. Consequently, a major focus of my research was to understand the mechanism by which PS is transported from its site of synthesis in an ER domain — mitochondria-associated membranes, or MAM — to mitochondria for decarboxylation to PE.”
“Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation[S]” by Petra Kotzbeck, Antonio Giordano, Eleonora Mondini, Incoronata Murano, Ilenia Severi, Wiebe Venema, Maria Paola Cecchini, Erin E. Kershaw, Giorgio Barbatelli, Guenter Haemmerle, Rudolf Zechner and Saverio Cinti, 1 January 2018, Journal of Lipid Research.
“Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3[S]”
Hana Kimura, Kohei Arasaki, Yuki Ohsaki, Toyoshi Fujimoto, Takayuki Ohtomo, Junji Yamada and Mitsuo Tagaya, 1 January 2018, Journal of Lipid Research.
“Regulation of kynurenine metabolism by a ketogenic diet” by Svenja Heischmann, Lindsey B. Gano, Kevin Quinn, Li-Ping Liang, Jacek Klepacki, Uwe Christians, Nichole Reisdorph and Manisha Patel, 1 January 2018, Journal of Lipid Research.
“Thematic Review Series on the Living History of Lipids” by Merrill Alfred H. Jr., 1 November 2013, Journal of Lipid Research.