Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function, and by inhibiting or activating LPL, respectively. Therefore, these proteins play key role in plasma lipid metabolism, but their role in regulating LPL activity in human insulin resistant (IR) (i.e., pre-diabetic) state is not known. Thus, the purpose of this research was to evaluate the concentrations of ApoC3 and ApoC2 in plasma along with the endothelial-bound LPL availability and activity in IR humans and in healthy, insulin sensitive (IS)/control humans. Insulin resistance was evaluated from plasma insulin and glucose responses to an oral glucose tolerance test, and by calculating the Matsuda index. Subjects were placed in the following groups: IR subjects, Matsuda index <4.0 (N=7; 4 males, 3 females); IS, Matsuda index >7.0 (N=11, 9 males, 2 females). IR and IS subjects received an intravenous infusion of insulin (1 mU/kg/min and 0.5 mU/kg/min, respectively) for 30 minutes to stimulate LPL activity. Whole-body endothelial-bound LPL was released from the vasculature by intravenous infusion of heparin. Plasma samples were collected 10 minutes after heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations. Although plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P = 0.02), plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03). However, ApoC2 concentration was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). These findings suggest that circulating APOC3 and ApoC2 are not key determinants regulating LPL activity during hyperinsulinemia in the vasculature of insulin resistant humans.

Preliminary studies indicate that the use of dietary menthol may prevent excessive weight gain through the activation of the transient receptor potential melastatin family member 8 (TRPM8) ion channel. It has also been expressed that elevation of the core temperature (Tc) inducing mild hyperthermia via an increase in ambient temperature aids in a marked reduction of the drive to eat and weight gain. While caloric restriction (CR) aims to treat obesity and secondary sicknesses, weight regain is a common result during long term weight maintenance. The goal of these studies was to evaluate and identify if the menthol and mild hyperthermia mechanisms could couple synergistically to reduce or abrogate weight gain. Ambient temperature (Ta) was increased incrementally to identify the threshold in which rodents display mild hyperthermia. Our initial attempts at hyperthermia induction failed because of limitations in the environmental chamber. These trials fail to note a threshold at which elevated Tc is sustained for any period of time. The data suggests an ambient temperature of 36-38 °C would be appropriate to induce a mild hyperthermia. A mild hyperthermia is described as the elevation of Tc 2-3 ° above the hypothalamic set point. To facilitate future hyperthermia studies, an environmental chamber was designed. A wine cooler was converted to withstand the desired temperatures, through the use of heat tape, a proportional controller, and a translucent Plexiglas custom fit door. Beyond leveraging temperature to regulate weight gain, dietary changes including a comparison between standard chow food, high fat diet, and menthol supplemented chow food treatment illustrate a strong likelihood of weight gain variability. In this pilot study, weight gain expression when given a diet supplemented with menthol (1%) showed no statistical significance relative to a high fat diet nor chow food, however, it revealed a trend of reduced weight gain. It is assumed the combination of supplemental menthol and mild hyperthermia induction will exacerbate their effects.