Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans

Abstract

An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 ؎ 3.4% (SOL) and 164.2 ؎ 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ؎ 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r ‫؍‬ ؊0.98, P < 0.003) and SOL muscle (r ‫؍‬ ؊0.97, P < 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 ؎ 16.9% of baseline; P ‫؍‬ 0.005), but not in SOL muscle (to 114.4 ؎ 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ؎ 5.6% of baseline (P ‫؍‬ 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

A family history of type 2 diabetes increases risk factors associated with overfeeding

“…This is consistent with previous studies of short-term (3-days) [15] and long-term 272 (4.5-months) overfeeding [32] in healthy lean men. Our initial hypothesis was that FH+ 273 would have greater metabolic defects associated with overfeeding.…”

“…In humans, this model was previously applied in 63 lean healthy individuals. The observed outcomes from these studies include increases in 64 fasting insulin and glucose [12], increases in energy expenditure [13] and intramyocellular 65 triacylglycerol content [14] and decreases in peripheral [15] and hepatic insulin sensitivity 66 [12]. The aim of the present study was to examine prospectively the effects of 3 and 28-days 67 of overfeeding on body weight, fat distribution and insulin sensitivity and the relationships 68 between these factors in healthy individuals with and without a family history of type 2 69 diabetes.…”

Role of proton MR for the study of muscle lipid metabolism

“…This observation led to many studies that investigated the effect of short-term diet on IMCL concentrations (17,20,36,(51)(52)(53)(54)(55). It could be shown that the amount of fat in the diet strongly influences the replenishment of IMCL (17).…”

“…In a combined study of 1 H-and 13 C-MRS, Décombaz et al (36) were able to follow the replenishment of the two major energy supplies in skeletal muscle, IMCL and glycogen, under the influence of different diets. A well-controlled type of diet has been investigated in studies with the infusion of lipids and free fatty acids (54,(56)(57)(58). A study of (a) intravenous lipid infusion and hyperinsulinemia, (b) hyperinsulinemia alone or (c) intravenous lipid infusion without concomitant insulin infusion showed a marked steady increase of IMCL levels when lipid infusion and hyperinsulinemia are combined [protocol (a)].…”

Insulin and hyperandrogenism in women with polycystic ovary syndrome

“…Most women with PCOS present increased circulating levels of free fatty acids (FFAs), which have been shown to cause insulin resistance in vivo [79,80]. In fact, several in vivo studies demonstrated that elevating circulating FFAs leads to peripheral tissue insulin resistance [81][82][83]. Accumulation of plasma fatty acids in muscle and liver tissues induce mitochondrial dysfunction, oxidative stress, inflammation and immune disorders [84].…”