ISIS Report 25/02/13

Fructose and Overeating - Fuelling the Obesity Epidemic

A new brain imaging study finds fructose, but not glucose, causes distinct brain activity associated with a lack of fullness and satiety Dr. Eva Sirinathsinghji

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A new study finds that fructose consumption has distinct effects on brain regions that regulate appetite, a possible mechanism for ‘ever-eating’ and the widespread rise in obesity and other related disorders.

The study, led by Dr Robert Sherwin at Yale University in the US, used magnetic resonance imaging (MRI) techniques to look at the activity of brain regions associated with appetite and reward systems, to assess how they respond to fructose versus glucose [1].

Dramatic increase in fructose consumption correlated with obesity & diabetes

Increases in fructose consumption have risen dramatically since the creation of high fructose corn syrup (HFCS). HFCS has largely replaced table sugar as the most common industrial sweetener, especially in the US where most processed foods including soft drinks contain high levels of the sugar substitute. Industrial-scale, cheap over-production of corn since the Nixon era in the early 1970s laid the foundations for the wide-spread use of HFCS, and this continues today with the US devoting roughly a quarter of its agricultural land to corn crops, the majority of which are now genetically modified (GM).              

Rise in HFCS consumption over the last few decades appear to correlate with the sharp increase in obesity and other diet-related disorders including diabetes, suggesting fructose as a major contributory factor.  The HFCS used in beverages is usually 55 % fructose and 41 % glucose (HFCS55). Since its introduction, higher quantities of HFCS than sucrose is added despite it being sweeter (sucrose is a disaccharide of both fructose and glucose). The excessive consumption of fructose is therefore considered a major health risk.

Brains respond differently to fructose

In the new study, 10 people consumed fructose or glucose drinks 15 minutes before their brains were analysed for cerebral blood flow, an indirect measure of brain activity. They then mapped out the regions of the brain with significantly reduced blood flow; very different patterns emerged with the two sugars (Figure 1).

Figure 1   Reduced cerebral blood flow (marked in blue) after glucose (upper panel) and fructose ingestion at different sections of the brain on fMRI

Glucose lowered cerebral blood flow in the hypothalamus, a region that controls appetite and fuel sensing and regulates hunger, among other metabolic processes including thirst, and circadian rhythm. Glucose also reduced activity in other brain regions that are thought to act in synchrony to read a person’s metabolic state and drive motivation and reward - the thalamus, insula, anterior cingulate and striatum.

Fructose reduced activity in the posterior thalamus, the posterior cingulate cortex, fusiform gyrus, visual cortex and the hippocampus, a region most noted for its role in learning and memory and mediates emotional responses to food. Hippocampal activity in rodents has previously been associated with inhibition of feeding behaviour. Functional connectivity after fructose consumption only increased between the hypothalamus and the thalamus.

Functional connectivity analysis was also carried out to identify brain regions that are temporally and thus functionally related. Again the two sugars gave very different patterns (Figure 2).

Figure 2   Functional connectivity increase (bright yellow and red patches) after glucose (upper panel) and fructose (lower panel) at different optical sections of the brain

Glucose increased functional connectivity between the hypothalamus and the striatum and thalamus, other regions involved in feeding behaviour. Fructose on the other hand, only increased functional connectivity between the hypothalamus and the thalamus.

Behavioural testing of the participants found that fructose led to reduced feelings of both satiety and fullness.

Metabolic experiments found glucose but not fructose, to induce a significant rise in blood insulin, a hormone that acts centrally to induce satiety and dampen reward value of food. Lastly, they were able to detect fructose in the brain of rodents following peripheral infusion of fructose, showing its ability to penetrate the blood-brain barrier.

All together, these results indicate that the brain responds differently to fructose, leaving individuals feeling less fulfilled and therefore more susceptible to over-eating.

New study confirms previous findings

This study is not the first to establish a link between fructose and obesity/metabolic disorders. A long-term feeding study in rats found that a 6-month high fructose diet followed by a 2-week high fat diet led to weight gain resulting from the development of leptin resistance during the high fructose diet [2]. Leptin is a hormone released by adipose tissue as a satiety signal after eating. Fructose has also been shown to provoke feeding in rodents as well as reduce circulating satiety-related molecules including insulin and glucagon-like polypeptide 1 (GLP-1) [3].

Indeed, fructose has been used by scientists as a tool for generating diabetes and/or obesity animal models in research. Most recently, a primate model of diabetes was induced by a high fructose diet. The rhesus monkeys developed insulin resistance and many features of the metabolic syndrome, including central obesity, dyslipidemia (abnormal blood lipid levels e.g. cholesterol/fat) and inflammation within a short period of time; moreover, a subset of monkeys developed type-2 diabetes [4]. The authors went on to suggest that due to the ‘rapidity with which the metabolic changes occur’, that fructose consumption was a ‘practical and efficient’ system to adopt for such research studies.

Other research studies have shown that fructose is metabolised in a different way from glucose, with fructose having a higher propensity to be converted into body fat, a process called lipogenesis. Prolonged fructose, but not glucose consumption has been shown to induce de novo lipogenesis in the liver [5]. Similarly, it is thought to promote visceral over subcutaneous fat deposition, a more common feature of metabolic disorders including diabetes [6].

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