Saturated fats contain a carbon chain which is fully ‘saturated’ with hydrogen atoms, allowing for no carbon double bonds, unlike unsaturated fats. This structure makes the longer chained saturated fats solid at room temperature.
Levels of saturated fat in the body are related to diet and metabolism. Saturated fats are synthesised via lipogenesis from acetyl-CoA (i.e. from carbs), while they are catabolised via β-oxidation for energy. In the diet, sources of fat generally contain some saturated fat, although the proportion/type varies greatly; rich sources include fatty meats, dairy products and refined fats/oils (e.g. butter, lard and coconut oil) (see). Note, unlike lipogenesis, dietary saturated fat uniquely increases levels in the intestine first, before absorption.
What we eat hits the gut first. The gut contains both the largest collection of microbes (gut microbiota) and immune tissue (gut-associated lymphoid tissue) in the body, which interact reciprocally. Unlike sugars and amino acids, fats are not normally a major fuel for the gut microbiota, although they do alter the intestinal environment. In animal models, diets high in saturated fats (e.g. lard, tallow and dairy) or omega-6 (e.g. corn and sunflower oil) induce bacterial dysbiosis and inflammation, which can be opposed by omega-3s (fish oil) 3–5. Saturated fats may specifically induce an overgrowth of bile-resistant, sulfur-reducing bacteria (e.g. Desulfovibrio and Bilophila), with inflammatory potential 4,5. Further, in a Candida albicans colonisation model, diets high in saturated and omega-6 fats supported the growth of C. albicans (can metabolise fats), whereas coconut oil lowered C. albicans levels, presumably due to its antifungal properties 6.
|Effect of several foods on postprandial |
endotoxin (LPS) levels and NF-kB
binding in healthy volunteers.
The gut microbiota is separated from the rest of the body by the gut barrier (mucus and epithelium). Diet greatly influences the permeability (‘leakiness’) of the gut barrier to bacteria and their antigens (e.g. LPS/endotoxin). In animals and humans, high energy/fat meals induce a postprandial (0-5hr) increase in blood LPS 7–9, inflammation and oxidative stress 10–12, which can be blocked by adding orange juice, resveratrol or fibre 13–15. Several studies implicate saturated fat as the main culprit 5,7,9,16,17. For instance, in humans, blood LPS was increased by 30g of cream (70% sat fat), but not orange juice or glucose (see fig) 11. In swine and humans, blood LPS was increased by a porridge-based meal made with coconut oil (15% sat fat) but decreased with fish oil (0.5% omega-3), while there was no significant effect with vegetable oils 16,17. However, with these meals, there was no effect on blood inflammatory markers 17.
Some potential mechanisms have been identified by which high fat diets may increase intestinal permeability. This may involve a transcellular (through cell) route, whereby fats can increase enterocyte membrane permeability (via lipid rafts 16) and intracellular transport via chylomicrons 7. And also a paracellular (between cells) route, whereby high fat diets can increase bile secretion which can decrease epithelial integrity 18 and colonic tight junction expression 19.
|LPS, aka. endotoxin|
LPS binds to toll-like receptor 4 (TLR4), expressed on the surface of many cell types, to activate inflammatory signaling. LPS (lipopolysaccharide) is so named because it contains fat (lipid) and carbohydrate (polysaccharide) (see fig). Saturated fats (C12-14) acylated in the lipid A portion of LPS are essential for signaling via TLR4; and similarly for lipopeptide signaling via TLR2 20. Moreover, free saturated fats (e.g. palmitic and lauric acid) can directly stimulate TLR4/2 signaling (via receptor dimerization and translocation into lipid rafts), which can be inhibited by DHA (omega-3) 20–23. Similarly, palmitic acid primes/activates the intracellular NF-kB and NLRP3 inflammasome pathways, while DHA inhibits them 24.
Direct modulation of inflammatory signaling by fatty acids could have relevance to many body tissues. In the gut, free fatty acids (FFAs) are liberated during digestion (by pancreatic lipase). Systemically, diet/metabolism influences cell membrane lipid composition and release of FFAs into blood by adipose tissues. In animal models, a high fat diet induces the loss of gut neurons and dysmotility (constipation) via LPS and saturated fat-mediated TLR4 signaling 25. In humans, elevated blood FFAs are seen in many metabolic diseases, with their deleterious effects (incl. inflammation and insulin resistance) attributable to saturated fat content (e.g. palmitate and stearate) 26. Saturated FFAs can also cross the blood-brain barrier, impair neuronal energy metabolism 27 and activate astrocytes (neuroinflammation) 23.
Beyond just inflammation, saturated fats have been linked to autoimmune disease. Fats can modulate T and B cells via indirect (e.g. gut microbiota) and direct mechanisms (e.g. signaling pathways). For instance, LPS/TLR4 signaling promotes Th17 activity and worsens experimental autoimmune encephalomyelitis (EAE) 28, an animal model of brain inflammation and multiple sclerosis (MS). Similarly, another study showed that dietary long-chain saturated fats (palmitic and lauric acid) promoted Th1/Th17 activity and worsened EAE 29. Interestingly, this effect involved suppression of intestinal short-chain fatty acids (SCFAs), which can induce Tregs and improve EAE 29. In humans, Dr Swank published repeatedly on a link between animal/saturated fat and MS, including the long-term effect of a low fat diet on disease activity (YouTube). More recently, a low cholesterol diet was also shown to lower autoimmune potential (Th17/Treg balance) in people with hepatitis C 30.
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