How Overconsuming Calories Create Excess Inflammation and Reprogram the Immune System


Everyone knows that a diet rich in calories, refined carbs and sugars, and fats/oils isn’t optimal for health. “The consumption of Western-type calorically rich diets combined with chronic overnutrition and a sedentary lifestyle in Western societies evokes a state of chronic metabolic inflammation, termed metaflammation,” explains Professor Eicke Latz, a director of the Institute of Innate Immunity at the University of Bonn in as a senior co-author in Immunity Cell Press, 2019.

Inflammation: The Good

Immune cells release inflammatory chemicals called cytokines. Cytokines are normally adaptive in nature. Adaptive means that it restores homeostasis (or balance) by clearing out a threat, which can be anything the immune system recognizes as foreign or in need of repair.

“Intact inflammatory pathways are critical for the health of tissues and proper homeostasis.”

Inflammation also harms nearby healthy cells in the process. The good news is that this can later be repaired by the immune system once the threat is cleared. Pro-inflammatory cytokines are then cleared and synthesis of anti-inflammatory cytokines is initiated — resolving the inflammation.

As Gökhan Hotamışlıgil, professor of metabolism at Broad Institute of MIT and Harvard, explains in Nature Reviews, “Intact inflammatory pathways are critical for the health of tissues and proper homeostasis, including the health of adipose tissue expansion in response to caloric excess.”

A skin wound repairs itself after swelling and redness first — that’s an example of how immune cells prioritize eliminating the threat before cell repair. Acute/temporary inflammation from consuming excess calories or a Western meal periodically is, thus, reversible once the ‘threat’ is cleared and anti-inflammatory cytokines kick in.

Inflammation: The Bad

The problem arises when the threat is never cleared, either because the immune system became ineffective or the threat keeps incoming, or both.

This keeps the immune system busy releasing pro-inflammatory cytokines for long periods — overdriving the immune system to the state of metaflammation (or chronic metabolic inflammation).

“Resolution of the inflammatory response leads to regeneration,” Arin Aurora, assistant professor at the University of Texas explained in Cell Stem Cell. “Chronic inflammatory cell activation [on the other hand] perpetuates tissue damage and hampers repair.”

Why is Caloric Overload Inflammatory?

What is a Western diet first? Professor Latz describes it as being rich in calories, refined sugars and fats/oils, processed meats, food additives, and salt. It’s also low in fibres, vitamins, minerals, and polyphenols. The Western diet has high glycemic indexes that lead to the rapid rise in insulin and subsequent absorption of calories into adipose tissues, Professor Latz says.

And these features of a Western meal induce unpleasant metabolic changes:

  • Excess sugars oxidize LDL cholesterol, which became highly reactive and damage surrounding tissues. Oxidized LDL also delivers excess cholesterol into the lysosomes of cells — overloading and damaging cells.
  • When fat cells (adipocytes) uptake excessive calories, it becomes insulin resistant to refuse incoming energy. The body reacts by secreting more insulin to force adipocytes to absorb more calories. The resulting lipid accumulation inside adipocytes damages the cell.
  • Delivering excess calories from sugars and fats into the gut microbiota provides extra nutrients that allow pathogenic microbes the chance to grow. Toxins production within the gut lumen then increases which leaks into the blood circulation and causes metabolic endotoxemia.
  • High blood sugar levels induce “epithelial reprogramming” in such a way that loosens tight junctions of the gut barrier — leading to leaky gut and gut inflammation.
  • Oversupply of omega-6 fats, mainly from soybean oil in processed foods, compete with the anti-inflammatory effects of omega-3 fats. In modern civilization, the ratio of omega-6 to omega-3 fats is about 20:1 — far exceeding the hypothetical ideal ratio of 3:1 or 1:1. This omega imbalance promotes a net pro-inflammatory state.

All the above represent some sort of threat that damages cells and tissues. The immune system then comes to deal with the threat (or cells in need of repair) by initiating inflammation. Since the threat becomes habitual, inflammation is never properly resolved.

“The Western diet appears to be mistakenly recognized by the immune system as a threat to the organism.”

This leads to a chronic spillover of pro-inflammatory cytokines that pushes the body into a constant state of DNA and mitochondrial damage, oxidative stress, and inflammation in many organs and tissues.

Western Diet Reprogram the Immune System

“Inflammatory triggers [of the Western diet], such as lipid metabolites (e.g., oxidized LDL), high amounts of glucose, glycation end products, fatty acids, or microbiome-associated metabolites can induce trained immunity,” Professor Latz says. Trained immunity is when the immune system undergoes epigenetic reprogramming to “allow innate immune cells to respond to future challenges in an altered fashion,” the professor explains.

What is the altered fashion? In response to unresolved inflammation, immune cells secrete more pro-inflammatory cytokines to prepare for future challenges. The unresolved inflammation also signals the bone marrow to make more immune cells to prepare for future challenges. These newly made immune cells are also enhanced with inflammatory capacity.

The Irony Between Metaflammation and Pathogen Defence

Trained immunity is like immunological memory in pathogen defense — wherein encountering the same pathogen the second time results in a stronger immune reaction to eliminate it before it any symptoms appear.

Likewise, the immune system keeps a memory of its response to the Western diet and initiates a stronger immune response the next time it confronts the same stimulus (or threat). In this way, Professor Latz says that, “The Western diet appears to be mistakenly recognized by the immune system as a threat to the organism.”

Except, this time, we don’t encounter the same pathogen 3–6 times/day every day for months and years. The mechanisms our immune system honed over evolution to fight infections, thus, become maladaptive in the context of the Western diet. It drives a “long-term chronic inflammatory state [and] tissue inflammation,” the professor says.

At the same time, the state of metaflammation consumes “immunological resources” that are limited. So while increasing resources are being used to deal with metaflammation, less is available for fighting microbial infections.

This explains why obese people are known to be more susceptible to infections, which “makes sense,” says Bente Klarlund Pederson, a professor of internal medicine at the University of Copenhagen. “Obese people have an immune system that is often plagued by inflammation,” she continued. “Research suggests that people who have chronic inflammation have a hard time fighting infections.”

To Close

The habitual consumption of the Western diet “causes metaflammation and is ‘memorized’ by innate immune cells through long-lasting metabolic and epigenetic cellular reprogramming,” Professor Latz summarized nicely.

The professor added that modern public health has done a great job of preventing early death from infectious diseases. But the accompanying Western lifestyle has fueled the development of chronic diseases that decrease the quality of life. “Chronic inflammation induced by excessive nutrient intake and metabolic syndrome [i.e., metaflammation] has reached epidemic proportions in the 21st century,” agrees Professor Mehmet Kanbay.

“Adherence to a low-risk lifestyle (no smoking, regular physical activity, moderate alcohol intake, and consumption of high-quality food) can be very effective and potentially extend life expectancy at age 50,” Professor Latz advised. Beware of the Western diet (or lifestyle) that overdrives and rewires the immune system to push the body into a state of metaflammation, he says.

Comments / 6

Published by

MSc Biology | 9x first-author academic papers | 280+ articles on coronavirus | Independent science writer


More from Shin

Comments / 0