High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects

Abstract

OBJECTIVETo evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state.RESEARCH DESIGN AND METHODSSubjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis.RESULTSBaseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05).CONCLUSIONSThese studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.

MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

“…Bacterial LPSs derived from the outer membranes of Gram-negative bacteria have been intensively studied and are known to induce metabolic endotoxemia by promoting secretion of pro-inflammatory cytokines (17). Studies in both animal models and humans have shown that a high-fat diet can modulate the gut microbiota and increase circulating levels of LPSs, probably by uptake of LPSs in chylomicrons secreted from intestinal epithelial cells or through increased intestinal permeability (17,18,19,20). Mice fed a diet rich in fat exhibited increased adiposity and lowgrade inflammation dependent on LPS signalling, and infusion of LPSs in mice resulted in metabolic changes comparable to the high-fat feeding.…”

Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages

“…LPS is not only present locally in tissues such as periodontium when infection with gram-negative bacteria occurs; it also exists systematically in blood circulation at low concentrations (21). Interestingly, clinical studies have shown that circulating LPS is increased in patients with obesity (21,33), and animal studies have shown that TLR4 deficiency in mice protects against the development of insulin resistance (41).…”

“…Interestingly, clinical studies have shown that circulating LPS is increased in patients with obesity (21,33), and animal studies have shown that TLR4 deficiency in mice protects against the development of insulin resistance (41). Taking these clinical and animal findings together, it is indicated that TLR4 signaling triggered by low concentrations of LPS may contribute to the inflammatory state that is essential for developing insulin resistance (50).…”

Dietary lipid emulsions and endotoxemia

“…Mixed hyperlipidic/hyperglucidic meals (51 g lipids, 81 g carbohydrates) also increase plasma LPS in the postprandial phase in healthy lean men (Ghanim et al, 2009. Recent studies confirm these results of postprandial endotoxemia in type 2 diabetic subjects consuming 75 g of lipids (Harte et al, 2012) and in morbidly obese subjects consuming a 50 g lipid load (Clemente-Postigo et al, 2012). Among postprandial studies, some used dairy fat (butter or cream), other used mixed fatrich foods (often eggs and sausage) or simple oil load or, in the form of single food or into mixed meals, and altogether fat intake was high (Tab.…”