In Muscle-Specific Lipoprotein Lipase−Overexpressing Mice, Muscle Triglyceride Content Is Increased Without Inhibition of Insulin-Stimulated Whole-Body and Muscle-Specific Glucose Uptake

Abstract

In patients with type 2 diabetes, a strong correlation between accumulation of intramuscular triclycerides (TGs) and insulin resistance has been found. The aim of the present study was to determine whether there is a causal relation between intramuscular TG accumulation and insulin sensitivity. Therefore, in mice with musclespecific overexpression of human lipoprotein lipase (LPL) and control mice, muscle TG content was measured in combination with glucose uptake in vivo, under hyperinsulinemic-euglycemic conditions. Overexpression of LPL in muscle resulted in accumulation of TGs in skeletal muscle (85.5 ؎ 33.3 vs. 25.7 ؎ 23.1 mol/g tissue in LPL and control mice, respectively; P < 0.05). During the hyperinsulinemic clamp study, there were no differences in plasma glucose, insulin, and FFA concentrations between the two groups. Moreover, wholebody, as well as skeletal muscle, insulin-mediated glucose uptake did not differ between LPL-overexpressing and wild-type mice. Surprisingly, whole-body glucose oxidation was decreased by ϳ60% (P < 0.05), whereas nonoxidative glucose disposal was increased by ϳ50% (P < 0.05) in LPL-overexpressing versus control mice. In conclusion, overexpression of human LPL in muscle increases intramuscular TG accumulation, but does not affect whole-body or muscle-specific insulinmediated uptake, findings that argue against a simple causal relation between intramuscular TG content and insulin resistance.

Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits

“…These findings in transgenic rabbits contrast with the results in transgenic mice that showed insulin resistance accompanied by accumulation of TG in their skeletal muscle [16] or liver [4]. Nevertheless, one study reported that there is no effect of the accumulation of TG in skeletal muscle on insulin-stimulated whole-body and muscle-specific glucose uptake [18]. Another study [17] found no difference in the muscle TG contents between musclespecific LPL transgenic and control mice, in spite of transgenic mice having a state of insulin resistance.…”

“…However, studies on transgenic mice have also generated conflicting results regarding the effects of LPL on insulin resistance. For example, two studies on LPL transgenic mice have shown that overexpression of human LPL in mouse muscle is associated with insulin resistance [4,17], whereas one group (even using the same transgenic mice as in the above study) failed to show a correlative or causal relationship between increased LPL activity and insulin resistance even though there was increased TG content in the muscles [18]. In addition, one study reported that LPL transgenic mice were protected against diet-induced obesity regardless of slight hyperglycaemia [16].…”

“…One of the best experimental approaches is to use transgenic animals that overexpress LPL. Several lines of transgenic mice that overexpress human LPL have been created, and although the sites of overexpression differ, all transgenic mice show decreased plasma levels of TG [4,13,14,15,16,17,18]. However, studies on transgenic mice have also generated conflicting results regarding the effects of LPL on insulin resistance.…”

Effects of dietary lipids and Clostridium butyricum on serum lipids and lipid-related gene expression in broiler chickens

“…lipid-related genes expression Lipid, C. Butyricum LPL is responsible for the hydrolysis of plasma lipoproteins, a rate-limiting step in lipid transport into peripheral tissues (Goldberg, 1996). Overexpression of muscle LPL has been associated with increasing intramuscular triacylglycerol accumulation and fat deposition in mammals (Voshol et al, 2001). Although no significant difference in LPL expression in breast muscle was found in broilers fed the diet supplemented with C. butyricum, a trend toward upregulated LPL gene expression was found, and LPL activity in muscle tissue was significantly increased by C. butyricum addition.…”

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

“…The IMCL content, which in many [1][2][3][4] but not all studies [45,46] has been shown to be increased in insulin resistance, was also one focus of our experiments. The effects of TGRLs on insulin signalling and glucose homeostasis followed a time-dependent fashion.…”