A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal

Abstract

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20–25 kg/m2) and 18 obese (BMI: >30 kg/m2) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial

“…Up to date, only one study tested different fat amounts of 34 -102 g fat (in 500 -1500-kcal meals) and showed no difference in the dose-response of postprandial endotoxemia between normal-weight and insulin-resistant obese subjects (BMI ϭ 39 kg⅐m Ϫ2 ) (17). We reveal that in nonmorbid obese subjects (BMI ϭ 32 kg⅐m Ϫ2 ), compared with NW, postprandial endotoxemia increases with fat amount in the meal proportionally to chylomicronemia.…”

Comparisons of the Postprandial Inflammatory and Endotoxaemic Responses to Mixed Meals in Young and Older Individuals: A Randomised Trial

“…Inflammatory gene expression [16], plasma cytokines [18], and endotoxaemia [25] are reported to be particularly elevated after high-fat or high-caloric meals [55] in metabolically-compromised adults, such as those with T2DM and metabolic syndrome. These acute meal responses may contribute to a state of chronic low-grade inflammation, accelerating the development of insulin resistance and cardiovascular disease through progression of atherosclerosis [56,57].…”

Dairy products and inflammation: A review of the clinical evidence

“…The specific reactivity of the MET group may be linked mechanistically to the inflammatory nature of obesity. Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of inflammatory cytokines (Guri and Bassaganya-Riera, 2011;Schwander et al, 2014). As low-grade systemic inflammation links obesity to metabolic pathologies, including insulin resistance, cardiovascular diseases, or type-2 diabetes, targeting obesity-related inflammatory components may be a useful preventive strategy.…”

“…In particular, integrating the variable 'dose' into study designs could allow researchers to draw a causal relationship between the food investigated and the physiological response measured in humans (Schwander et al, 2014). Also, although dozens of nutrients with immunomodulatory activity have been proposed in the literature (Ballard and Morrow, 2013), the bioactive nutrients potentially modulating inflammation in the reviewed studies, remain largely unknown even considering animal studies.…”