THE LABORATORY OF JANET KING, PHD

Dr. King’s research focuses on metabolic adjustments to changes in nutrient intakes in humans; she is especially interested in metabolism and nutrient utilization of pregnant and lactating women. Nutrients of interest include zinc, calcium, and energy. King has discovered that 1) the increased needs for zinc and calcium during pregnancy are met, in part, by an increase in the efficiency of absorption, 2) that individuals adapt to low intakes of zinc by increasing the efficiency of zinc absorption, reducing zinc excretion, and conserving tissue zinc in slowing turning over tissues such as the bone and muscle, and 3) that excessive fat stores in women at conception alters hormonal concentrations and raises the rates of energy expenditure at rest.

To accomplish her studies of zinc metabolism, Dr. King developed tracer methods using kinetic models and stable (not radioactive) isotopes, which are now used world-wide. She employs similar techniques to study calcium, carbohydrate, and lipid metabolism.

RESEARCH INTERESTS

Introduction
We are interested in determining how the body adjusts metabolic pathways and physiological functions when nutrient intakes are insufficient or when demands increase, such as in pregnancy. Our studies have focused on zinc, calcium, and energy metabolism in healthy adults and pregnant women. We have shown that the body makes multiple adjustments in nutrient utilization (i.e., rates of absorption, excretion, and tissue distribution) to maintain nutrient homeostasis when intakes are low. But, intakes below a certain threshold compromise physiological functions. That threshold can be raised by the individual’s health (i.e., obesity, malabsorptive disease, oxidative stress) or by the type of diet consumed (i.e., plant- or animal-based). In other words, the nutritional needs of individuals are altered by their diet and state of health. We are beginning to evaluate the effect of genetics on nutritional needs as well.

Metabolic Adjustments to Zinc Deficiency
About one-half of the world’s population consumes diets that are insufficient in zinc. Low zinc intakes are associated with stunting, or growth retardation, in children and an increased susceptibility to infections. Disadvantaged populations around the world subsist primarily on cereal-based diets, which are high in phytate, a compound that binds zinc and reduces its absorption. Furthermore, their intake of good sources of zinc, shellfish and red meat, is limited. Using kinetic models and stable isotopic tracers of zinc, we found that zinc absorption and endogenous excretion fall dramatically when zinc intakes are insufficient [1]. But, those adjustments do not prevent a decline in plasma zinc concentrations because zinc is sequestered in slowing turning over tissues, such as bone and muscle [2-4]. This sequestration of zinc makes less available for zinc-demanding functions such as growth and immunity. The response to zinc deficiency is quite variable among individuals, however. We think that genetics influences a person’s response to zinc depletion. We are currently evaluating the effect of zinc depletion on the genetic expression of two proteins involved in zinc metabolism, metallothionein 1 and zinc transporter protein 1. Phytate, the phosphorus storage compound in cereals, reduces zinc absorption [5, 6] . We are also investigating the effect of a small amount of beef, which contains a factor that improves zinc absorption, on the absorption of zinc from beans, a stable in the Mexican diet. In the future, we also plan to study the effect of changes in zinc status on DNA integrity and gene expression.

Adjustments in Calcium and Zinc Metabolism during Pregnancy and Lactation
The need for calcium and zinc increases during pregnancy to support fetal growth and development; the needs are particularly high during the last trimester when fetal growth is most rapid. In a longitudinal study of healthy pregnant women consuming good diets, we found that the efficiency of calcium and zinc absorption increased in late pregnancy. In lactation, calcium needs were met by mobilization of bone mineral and reduced urinary losses while a further increase in zinc absorption provided the zinc need [7-9]. The effect of maternal calcium and zinc intake on the adjustments made in pregnancy was studied in two groups of women consuming diets low in those minerals, a group of Southeast Asian immigrants to California and a group of Brazilian women. The efficiency of calcium and zinc absorption was much higher in these women, but the total amount of mineral absorbed was lower suggesting that the amount of calcium and zinc provided to the fetus was reduced. Pregnant women world-wide are advised to take an iron supplement. In our longitudinal study of California women [7], we found that supplemental iron reduced zinc absorption during lactation. We are currently completing a study to determine if the negative effect of iron on zinc absorption can be avoided by taking the iron supplements at bedtime.

Energy Metabolism in Lean and Obese Pregnant Women
It is estimated that pregnant women need about 80,000 additional calories [10]. In a longitudinal study, we found that the changes in energy metabolism were quite variable among seemingly similar women [11]; women delivering larger babies tended to gain less fat during pregnancy and have larger increases in resting energy expenditure. We also observed that obese women had much higher rates of resting energy expenditure than did lean women [12]; the more obese the woman, the greater the rate of energy expenditure. We subsequently showed that the marked increase in energy expenditure among obese pregnant women was related to circulating leptin concentrations (a hormone secreted by adipocytes and placental tissue). Although obese women seem to waste energy by this large increase in their resting energy expenditure in pregnancy, they still have larger babies than do lean women. Maternal blood glucose is the primary fuel for the fetus. We hypothesize that obese women have higher blood glucose levels that provide excessive fuel to the fetus and increases fetal growth. We plan to test that hypothesis by comparing the metabolic response to a low and high glycemic diet in obese pregnant women.

Obesity and Mineral Metabolism
Obesity is attributed to an excessive supply of energy. We hypothesize, however, that the quality of the diet also influences appetite and energy metabolism. To test that hypothesize, we evaluated the effects of a calcium supplement on body fat and rates of lipolysis in overweight women. There were no effects on the rates of fat oxidation and breakdown. But, the women tended to lose body fat and the activity of fatty acid synthease in adipose tissue tended to decline. We plan to further investigate the effects of zinc and calcium on glucose and lipid metabolism in experimental animals.