Brain activity and connectivity changes in response to glucose ingestion.

Objectives: The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast.Methods: Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50 g/300 ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity.Results: Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex.Discussion: Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward.Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.

Effect of flavor on neuronal responses of the hypothalamus and ventral tegmental area.

Although it is well known that food intake is affected by the palatability of food, the actual effect of flavoring on regulation of energy-homeostasis and reward perception by the brain, remains unclear. We investigated the effect of ethyl-butyrate (EB), a common non-caloric food flavoring, on the blood oxygen level dependent (BOLD) response in the hypothalamus (important in regulating energy homeostasis) and ventral tegmental area (VTA; important in reward processes). The 16 study participants (18-25 years, BMI 20-23 kg/m2) drank four study stimuli on separate visits using a crossover design during an fMRI setup in a randomized order. The stimuli were; plain water, water with EB, glucose solution (50gram/300 ml) and glucose solution with EB. BOLD responses to ingestion of the stimuli were determined in the hypothalamus and VTA as a measure of changes in neuronal activity after ingestion. In the hypothalamus and VTA, glucose had a significant effect on the BOLD response but EB flavoring did not. Glucose with and without EB led to similar decrease in hypothalamic BOLD response and glucose with EB resulted in a decrease in VTA BOLD response. Our results suggest that the changes in neuronal activity in the hypothalamus are mainly driven by energy ingestion and EB does not influence the hypothalamic response. Significant changes in VTA neuronal activity are elicited by energy combined with flavor.

Dietary sugars and non-caloric sweeteners elicit different homeostatic and hedonic responses in the brain.

OBJECTIVE: The brain is essential in regulating intake of food and beverages by balancing energy homeostasis, which is regulated by the hypothalamus, with reward perception, which is regulated by the ventral tegmental area (VTA). The aim of this study was to investigate the effects of ingestion of glucose, fructose, sucrose, and sucralose (a non-caloric artificial sweetener) on the magnitude and trajectory of the hypothalamic and the VTA blood oxygen level-dependent (BOLD) responses. METHOD: In five visits, 16 healthy men between 18 to 25 y of age with a body mass index between 20 and 23 kg/m2 drank five interventions in a randomized order while a functional magnetic resonance imaging scan was taken. The interventions consisted of 50 g of glucose, fructose, or sucrose, or 0.33 g of sucralose dissolved in 300 mL tap water. The control condition consisted of 300 mL of plain tap water. BOLD signals were determined in the hypothalamus and the VTA within a manually drawn region of interest. Differences in changes in BOLD signal between stimuli were analyzed using mixed models. RESULTS: Compared with the control condition, a decrease in BOLD signal in the hypothalamus was found after ingestion of glucose (P = 0.0003), and a lesser but delayed BOLD response was found after ingestion of sucrose (P = 0.006) and fructose (P = 0.003). Sucralose led to a smaller and transient response from the hypothalamus (P = 0.026). In the VTA, sucralose led to a very similar response to the water control condition, leading to an increase in VTA BOLD activity that continued over the measured time period. The natural sugars appeared to only lead to a transient increase in VTA activity. CONCLUSIONS: Glucose induces a deactivation in the hypothalamus immediately after ingestion and continued over the next 12 min, which is correlated with satiety signaling by the brain. Fructose and sucrose are both associated with a delayed and lesser response from the hypothalamus, likely because the sugars first have to be metabolized by the body. Sucralose leads to the smallest and most transient decrease in BOLD in the hypothalamus and leads to a similar response as plain water in the VTA, which indicates that sucralose might not have a similar satiating effect on the brain as the natural sugars.

The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit.

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.

No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers.

Intake of flavonoids is associated with a reduced cardiovascular risk. Oxidation of LDL is a major step in atherogenesis, and antioxidants may protect LDL from oxidation. Because tea is an important source of flavonoids, which are strong antioxidants, we have assessed in a randomized, placebo-controlled study the effect of consumption of black and green tea and of intake of isolated green tea polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and lipids. Healthy male and female smokers (aged 34+/-12 years, 13 to 16 per group) consumed during a 4-week period 6 cups (900 mL) of black or green tea or water per day, or they received as a supplement 3.6 grams of green tea polyphenols per day (equivalent to the consumption of 18 cups of green tea per day). Consumption of black or green tea had no effect on plasma cholesterol and triglycerides, HDL and LDL cholesterol, plasma vitamins C and E, beta-carotene, and uric acid. No differences were found in parameters of LDL oxidation. Intake of green tea polyphenols decreased plasma vitamin E significantly in that group compared with the control group (-11% P=.016) but had no effect on LDL oxidation ex vivo. We conclude that consumption of black or green tea (6 cups per day) has no effect on plasma lipids and no sparing effect on plasma antioxidant vitamins and that intake of a high dose of isolated green tea polyphenols decreases plasma vitamin E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in vitro, no effect was found on LDL oxidation ex vivo after consumption of green or black tea or intake of a green tea polyphenol isolate.

In vitro production of monoclonal antibodies under serum-free conditions using a compact and inexpensive hollow fibre cell culture unit.

A compact and easily portable hollow fibre cell culture system using commercially available components is described. The construction is relatively cheap and simple. As the hollow fibre cell culture cartridge we chose an inexpensive haemodialyser. Though not specially developed for this purpose this performed excellently in our system. Using a serum-free medium supplemented with ethanolamine, selenium and transferrin, an average antibody production of 30-200 mg per cartridge per day could be achieved, depending on the cell line. Because a serum-free medium was used, monoclonal antibodies could readily be purified on a large scale.

Effects of type and amount of dietary fat on rabbit and rat lymphocyte proliferation in vitro.

To investigate whether dietary linoleic acid inhibits lymphocyte proliferation, rabbits were fed diets containing 35% of the digestible energy (35 en%) as sunflower seed oil (25 en% linoleic acid) or palm oil (3.5 en% linoleic acid). No differences in the mitogen-induced proliferation of peripheral blood lymphocytes (PBL) or splenocytes or in the effect of sera on PBL proliferation were observed. To investigate whether the amount of dietary fat affects lymphocyte proliferation, rats were fed diets containing 10 or 35 en% as fat. No difference in the mitogen-induced proliferation of splenocytes was obtained. However, serum from fed rats but not from fasted rats of the 35 en% fat group inhibited splenocyte proliferation, in comparison with serum from rats of the 10 en% fat group. Removing chylomicrons from the sera did not affect proliferation. The very low density lipoprotein + chylomicron fraction of the plasma inhibited proliferation. The inhibition was stronger for the 35 en% fat group than for the 10 en% fat group and was increased by fasting. No systematic differences in the effects on proliferation were obtained with the low or high density lipoprotein fractions of both groups. Diets containing a high amount of linoleic acid do not inhibit lymphocyte proliferation. The amount of dietary fat might affect lymphocyte proliferation through one or more factors in the plasma.