LISBON, Portugal — Not all fat in the human body is exactly the same. The most harmful type of obesity involves having too much “deep” or visceral fat. However, having the right amount of this deep fat actually keeps the body healthy. Now, a new study reveals there’s more than just fat in that fat. Researchers in Portugal have discovered a hidden system in the body that helps burn off excess fat.
“Excess visceral fat is very dangerous and at the same time very difficult to eliminate,” explains Henrique Veiga-Fernandes, principal investigator and co-director at the Champalimaud Research Program, in a media release. “In this project, our team set out to explore the mechanisms that naturally reduce it, with the hope of uncovering potential clinical applications.”
Unlike soft fat stores which sit right under the skin, deep fat resides inside the abdominal cavity and envelops the vital organs. While normal amounts of visceral fat supports biological functions like reproduction, excessive amounts produce unhealthy levels of proteins and hormones that can damage human tissue and surrounding organs.
In their study of this substance in mice, researchers discovered the first known neuro-immune process that allows the brain to trigger immune functions inside visceral fat. The team believes this discovery may lead to a new treatment for obesity and weight-related illnesses.
A deeper look at ‘deep fat’
If you see visceral fat, it would look like a gooey, yellow mass however, it’s actually a much more complex tissue than that. Visceral fat contains fat cells, nerve fibers, and several other types of cells – including immune cells. When it comes to this new system, scientists are particularly interested in immune cells called ILC2s (Type 2 Innate Lymphoid Cells).
“ILC2s are essential for various immune functions in many tissues and organs, including maintaining the overall well-being of fat tissue. However, we didn’t know which cells control ILC2s in visceral fat and what molecular messages they use to communicate,” says study first author Ana Filipa Cardoso.
The study reveals that in the lungs, the nervous system directly controls what ILC2s do. The team expected this would be the same in deep fat, but they discovered something completely different.
“The neurons and the immune cells were not talking to each other,” Cardoso reports. “So we investigated other candidates in the tissue, finally coming across a rather unexpected ‘middleman.'”
Not just a middleman in your fat
Before this study, scientists thought this middleman of immune system communication in deep fat was just a bystander in a person’s body.
“Mesenchymal cells (MSCs) have been widely ignored until about one to two decades ago,” Veiga-Fernandes says. “The widespread view was that they mainly produced the scaffolding of the tissue, over which other cells would ‘do the work’. However, scientists have since discovered that MSCs carry out multiple essential active roles.”
In fact, experiments reveal both a “chain of command” and the molecular messages that pass from the brain to visceral fat.
“It starts with neural signals onto MSCs. MSCs then send a message to ILC2s, to which ILC2s respond by ordering fat cells to rank up their fat metabolism,” Cardoso explains.
“It’s as though the neural and immune cells don’t speak the same language, and the MSCs serve as an interpreter,” Veiga-Fernandes adds. “Taken within the larger context, it does make sense. MSCs effectively make up the tissue’s ‘ecosystem’, and so they are perfectly situated to fine-tune the activity of other cells.”
Tracking the signals to fat that keep people healthy
Study authors also looked at what causes all of this neural activity to take place inside deep fat and how it triggers fat burning in the body.
“The nerve fibers inside visceral fat belong to what is called the peripheral nervous system. It is in charge of various physiological processes, such as regulating blood pressure,” Cardoso continues. “But the peripheral nervous system is not the boss. It is driven by the central nervous system, to which the brain belongs. So we asked next ‘which brain structure is at the very top of the chain of command?'”
Results of the study show that a region within the hypothalamus is the source of these signals. This region, called the PVH, sits near the base of the brain and it controls all sorts of processes, from reproduction, to gastrointestinal, to heart functions.
“This finding is quite significant,” Veiga-Fernandes explains. “It’s the first clear example of a cross-body neuronal circuit that translates brain information into an obesity-related immune function. It also raises many new questions. For instance, what triggers the PVH to issue the ‘fat burning’ command? Is it something related to behavior, such as eating certain foods or exercising? Or is it dependent on internal metabolic signals? Or both? It’s a white canvas – we don’t know what it is, and it’s tremendously fascinating.”
The team believes their findings may lead to a neuroscience-based approach to visceral fat-burning and obesity treatment.
“The multistep axis we identified offers many access points into visceral fat metabolism. We can now start thinking about how to use this new knowledge to fight visceral obesity and hence reduce the risk of cardiovascular disease and cancer,” Cardoso concludes.
The findings appear in the journal Nature.