An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

Abstract

Medium-chain fatty acids (MCFA) are a directly and readily absorbed source of energy. Exposure early-in-life to increased MCFA levels might affect development and impact (lipid) metabolism later in life. We tested whether an increased MCFA intake early-in-life positively affects adult body composition and metabolic status when challenged by a western-style diet (WSD). Male offspring of C57Bl/6j mice and Wistar rats were fed a control diet (CTRL; 10 w% fat, 14% MCFA) or a medium-chain triglycerides (MCT) diet with 20% MCFA until postnatal (PN) day 42, whereupon animals were fed a WSD (10 w% fat) until PN day 98. Body composition was monitored by Dual Energy X-ray Absorptiometry (DEXA). In rats, glucose homeostasis was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT); in mice, the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. At autopsy on PN day 98, plasma lipid profiles, glucose, insulin, and adipokines were measured; organs and fat pads were collected and the adipocyte size distribution was analysed. Milk analysis in mice showed that the maternal MCT diet was not translated into milk, and pups were thus only exposed to high MCT levels from early weaning onward: PN day 16 until 42. Mice exposed to MCT showed 28% less fat accumulation vs. CTRL during WSD. The average adipocyte cell size, fasting plasma triglycerides (TG), and leptin levels were reduced in MCT mice. In rats, no effects were found on the adult body composition, but the adipocyte cell size distribution shifted towards smaller adipocytes. Particularly mice showed positive effects on glucose homeostasis and insulin sensitivity. Increased MCFA intake early-in-life protected against the detrimental effects of an obesogenic diet in adulthood.

Keywords: C57Bl/6j mice; Wistar rats; body composition; early life; infant nutrition; lactation; obesity; prevention; programming.

Figure 1

Experimental design of the rat and mouse study. Litters were randomized and culled on postnatal (PN) day two, and were exposed to a CTRL or MCT diet (n = 3 litters/diet). Male pups continued their respective diets after weaning (on PN day 21) until they were switched to a western style diet (WSD) on PN day 42. Body composition was monitored by dual X-ray absorptiometry (DEXA) at the indicated time points. Rats were equipped on PN day 65 with a jugular vein cannula to enable repeated stress-free blood sampling for the purpose of an intravenous glucose (GTT) and insulin (ITT) tolerance test on PN day 84 and 90, respectively.

Figure 2

Mouse study Development of body weight (BW), lean body mass (LBM), fat mass (FM), and relative fat mass (%BW) during the WSD challenge (PN 43–98) of male mice (panels (A–D), respectively) fed a CTRL (n = 12) or MCT diet (n = 8) in early life (PN day 2–42). Values are means ± SD; * p < 0.05; ** p < 0.01; *** p < 0.001 vs. CTRL.

Figure 3

Rat study Development of body weight (BW), lean body mass (LBM), fat mass (FM), and relative fat mass (%BW) during the WSD challenge (PN 43–98) of male rats (panels (A–D), respectively) fed a CTRL (n = 9) or MCT diet (n = 7) in early life (PN day 2–42). Values are means ± SD.

Figure 4

Panel (A) Frequency distribution of EPI adipocyte cell size in CTRL (n = 8; white bars) and MCT (n = 4; grey bars) mice on PN day 98; Panel (B) Frequency distribution of RP adipocyte cell size in CTRL (n = 4; white bars) and MCT (n = 2; black bars) rats on PN day 98. The tables show the mean depot weight and cell size. Values are means ± SD; * p < 0.05; *** p < 0.001 vs. CTRL; EPI, epididymal fat; RP, retroperitoneal fat.

Figure 5

Results of the intravenous GTT (panel (A) and (B)) and intravenous ITT (panel (C)) carried out on PN day 84 and 90, respectively, in male rats fed a CTRL (n = 11–12) or MCT diet (n = 7–8) in early life (PN day 2–42). Values are means ± SD.