Kathleen A. Page

The Effect of Depo Medroxyprogesterone Acetate (DMPA) on Cerebral Food Motivation Centers: A Pilot Study using Functional Magnetic Resonance Imaging

OBJECTIVE The primary objective is to examine activation of food motivation centers in the brain before and 8 weeks after depo medroxyprogesterone acetate (DMPA) administration. STUDY DESIGN This prospective experimental pilot study examined the effects of DMPA on food motivation centers utilizing functional magnetic resonance imaging (fMRI) in eight nonobese, ovulatory subjects. fMRI blood oxygen level dependent (BOLD) signal was measured using a 3-Tesla Scanner while participants viewed images of high-calorie foods, low-calorie foods and nonfood objects. fMRI scans were performed at baseline and 8 weeks after participants received one intramuscular dose of DMPA 150 mg. fMRI data were analyzed using the FMRIB Software Library. Changes in adiposity and circulating leptin and ghrelin levels were also measured. RESULTS There was a greater BOLD signal response to food cues in brain regions associated with food motivation (anterior cingulate gyrus, orbitofrontal cortex) 8 weeks after DMPA administration compared to baseline (z>2.3, p<.05 whole-brain analysis clustered corrected). No statistically significant change was detected in circulating leptin or ghrelin levels or fat mass 8 weeks after DMPA administration. CONCLUSION Analysis of differences in food motivation may guide the development of interventions to prevent weight gain in DMPA users. IMPLICATIONS These data support a neural origin as one of the mechanisms underlying weight gain in DMPA users and may guide future research examining weight gain and contraception.

The Vicious Cycle of Maternal Diabetes and Obesity: Moving From “What” to “How” and “Why”

See related article, p 941 a significant role of exposure to maternal diabetes in utero. The most compelling human evidence comes from studies in the Pima Indians, which have shown that offspring exposed tomaternal diabetes in utero have a 10-fold higher rate of childhood obesity, independent of maternal obesity and birth weight, than those not exposed to maternal diabetes. Importantly, the risk for obesity was shown to be higher in siblings born after their mothers developed diabetes than in those born before their mothers developed diabetes, providing strong evidence that in addition to genetics, there is an independent effect of the intrauterine environment on the risk for developing early-onset obesity. Studies in populations other than Pima Indians have demonstrated mixed results, with some, but not all, studies showing increased adiposity in offspring exposed to maternal diabetes in utero. One potential explanation for the lack of association between maternal diabetes and obesity in offspring in some studies is the inclusion of mothers who achieved optimal glucose control during pregnancy. Hillier et al examined the relationship between the level ofmaternal glycemia during pregnancy and the risk of obesity in amultiethnic cohort of 5to 7-year-old offspring of women with glucose levels ranging from normal to gestational diabetes, and found a continuous relationship between rising maternal glucose level and increased risk of obesity in offspring. They concluded that the level of fetal hyperglycemic exposure might be an important determinant in the risk for childhood obesity, confirming results from other groups. Their findings suggest that the risk of obesity in offspring could bemitigated by good glucose control. However, in a recent follow-up of children whose mothers participated in a randomized trial of treatment versus nontreatment of mild gestational diabetes mellitus, Gillman et al found that body mass index (BMI) at age 4 to 5 yearswas not lower in their treated group comparedwith their untreated group despite a lower mean birth weight and macrosomia rate in the treated group. The specific age at which height and weight are measured also may influence the results of relevant studies. In this issue of The Journal, Crume et al investigated the influence of in utero diabetes exposure on average BMI and BMI growth

Tracing the fate of fructose

The small intestine may shield the liver from the damaging effects of fructose. The small intestine may shield the liver from the damaging effects of fructose.

Taking a stand for metabolic health

Interrupting sitting with short bouts of walking improves glucose metabolism in overweight and obese children. Interrupting sitting with short bouts of walking improves glucose metabolism in overweight and obese children.

Faulty fat cells linked to weight gain

Altered fat cell lipolysis predicts long-term weight gain and risk of type 2 diabetes. Altered fat cell lipolysis predicts long-term weight gain and risk of type 2 diabetes.

Sustained obesity starts in early childhood

Accelerated weight gain during early childhood predicts sustained obesity. Accelerated weight gain during early childhood predicts sustained obesity.

Neural processing of food cues in pre-pubertal children: Neural food cue reactivity in children

Neuroimaging investigations of brain pathways involved in reward and motivation have primarily focused on adults. This study sought to identify brain responses to visual food cues and explore its relationships with adiposity and sex in pre‐pubertal children.

Effects of Physical Activity and Sedentary Behavior on Brain Response to High-Calorie Food Cues in Young Adults: Physical Activity and Brain Response to Food Cues

Physical activity (PA) promotes weight maintenance, potentially because of its beneficial effects on feeding behavior regulation via diminished food cue reactivity within brain reward regions. This study examined how levels of PA and sedentary behavior (SB) relate to brain responses to food cues.

Novel MRI methodology to detect human whole-brain connectivity changes after ingestion of fructose or glucose

A novel MRI protocol has been developed to investigate the differential effects of glucose or fructose consumption on whole-brain functional brain connectivity. A previous study has reported a decrease in the fMRI blood oxygen level dependent (BOLD) signal of the hypothalamus following glucose ingestion, but due to technical limitations, was restricted to a single slice covering the hypothalamus, and thus unable to detect whole-brain connectivity. In another previous study, a protocol was devised to acquire whole-brain fMRI data following food intake, but only after restricting image acquisition to an MR sampling or repetition time (TR) of 20s, making the protocol unsuitable to detect functional connectivity above 0.025Hz. We have successfully implemented a continuous 36-min, 40 contiguous slices, whole-brain BOLD acquisition protocol on a 3T scanner with TR=4.5s to ensure detection of up to 0.1Hz frequencies for whole-brain functional connectivity analysis. Human data were acquired first with ingestion of water only, followed by a glucose or fructose drink within the scanner, without interrupting the scanning. Whole-brain connectivity was analyzed using standard correlation methodology in the 0.01-0.1 Hz range. The correlation coefficient differences between fructose and glucose ingestion among targeted regions were converted to t-scores using the water-only correlation coefficients as a null condition. Results show a dramatic increase in the hypothalamic connectivity to the hippocampus, amygdala, insula, caudate and the nucleus accumben for fructose over glucose. As these regions are known to be key components of the feeding and reward brain circuits, these results suggest a preference for fructose ingestion.