TY - JOUR

T1 - High plasma triglyceride levels strongly correlate with low kisspeptin in the arcuate nucleus of male rats

AU - Overgaard, A

AU - Axel, A M

AU - Lie, M E

AU - Hansen, H H

AU - Mikkelsen, J D

PY - 2015/4

Y1 - 2015/4

N2 - OBJECTIVE: It is well known that reproductive capacity is lower in obese individuals, but what mediators and signals are involved is unclear. Kisspeptin is a potent stimulator of GnRH release, and it has been suggested that kisspeptin neurons located in the arcuate nucleus transmit metabolic signals to the GnRH neurons.METHODS: In this study, we measured body weight and plasma concentrations of leptin, insulin, testosterone, and triglycerides after high fat diet exposure and correlated these parameters with the number of kisspeptin-immunoreactive neurons in the arcuate nucleus of male rats. In this model, a high fat diet (45% or 60% energy from fat, respectively) or a control diet (10% energy from fat) was provided after weaning for three months.RESULTS: We find a significant increase in body weight and plasma leptin concentration, but no change in the number of kisspeptin-immunoreactive cells with increased fat in the diet. Kisspeptin-immunoreactive cells are not correlated with body weight, testosterone, leptin or insulin. However, we find that the number of kisspeptin-immunoreactive cells is strongly and negatively correlated with the level of plasma triglycerides (R2=0.49, p=0.004).CONCLUSION: We find a strong negative correlation between plasma triglyceride concentrations and the number of kisspeptin neurons in the rat arcuate nucleus regardless of the percentage of fat in the diet. In line with the lipotoxicity hypothesis, our results suggest that it is the level of hypertriglyceridemia per se that is a detrimental factor for kisspeptin expression in the arcuate nucleus.

AB - OBJECTIVE: It is well known that reproductive capacity is lower in obese individuals, but what mediators and signals are involved is unclear. Kisspeptin is a potent stimulator of GnRH release, and it has been suggested that kisspeptin neurons located in the arcuate nucleus transmit metabolic signals to the GnRH neurons.METHODS: In this study, we measured body weight and plasma concentrations of leptin, insulin, testosterone, and triglycerides after high fat diet exposure and correlated these parameters with the number of kisspeptin-immunoreactive neurons in the arcuate nucleus of male rats. In this model, a high fat diet (45% or 60% energy from fat, respectively) or a control diet (10% energy from fat) was provided after weaning for three months.RESULTS: We find a significant increase in body weight and plasma leptin concentration, but no change in the number of kisspeptin-immunoreactive cells with increased fat in the diet. Kisspeptin-immunoreactive cells are not correlated with body weight, testosterone, leptin or insulin. However, we find that the number of kisspeptin-immunoreactive cells is strongly and negatively correlated with the level of plasma triglycerides (R2=0.49, p=0.004).CONCLUSION: We find a strong negative correlation between plasma triglyceride concentrations and the number of kisspeptin neurons in the rat arcuate nucleus regardless of the percentage of fat in the diet. In line with the lipotoxicity hypothesis, our results suggest that it is the level of hypertriglyceridemia per se that is a detrimental factor for kisspeptin expression in the arcuate nucleus.

KW - Animals

KW - Arcuate Nucleus of Hypothalamus

KW - Biomarkers

KW - Diet, High-Fat

KW - Insulin

KW - Kisspeptins

KW - Male

KW - Obesity

KW - Rats

KW - Rats, Sprague-Dawley

KW - Testosterone

KW - Triglycerides

U2 - 10.4149/endo_2015_02_51

DO - 10.4149/endo_2015_02_51

M3 - Journal article

C2 - 25960005

VL - 49

SP - 51

EP - 57

JO - Endocrine Regulations

JF - Endocrine Regulations

SN - 1210-0668

IS - 2

ER -