Mechanism proposed for fructose syrup-obesity link
reported a possible mechanism that may explain the alleged link
between rising obesity and sweetened beverages.
The study could increase pressure on formulators to remove the ingredient from their products, with the use of high fructose corn syrup specifically accused of playing a major role in the rising obesity epidemic. Researchers from the University of Barcelona report that, according to their rat study, liquid fructose changes the metabolism of fat in the liver by impacting a specific nuclear receptor called PPAR-alpha, leading to a reduction in the liver's ability to degrade the sweetener. "Because PPAR-alpha activity is lower in human than in rodent liver, fructose ingestion in humans should cause even worse effects, which would partly explain the link between increased consumption of fructose and widening epidemics of obesity and metabolic syndrome," wrote the authors in the journal Hepatology. Metabolic syndrome (MetS) is a condition characterised by central obesity, hypertension, and disturbed glucose and insulin metabolism. The syndrome has been linked to increased risks of both type-2 diabetes and CVD. Fifteen per cent of adult Europeans are estimated to be affected by MetS, while the US statistic is estimated to be a whopping 32 per cent. According to figures published by the World Health Organisation (WHO), in the year 2015 some 2.3 bn adults will be overweight and more than 700 million will suffer from obesity, a pathology that is increasingly being seen in children. The researchers, led by Dr Juan Carlos Laguna, investigated the effects of feeding lab rats a fructose- or glucose-sweetened liquid (10 per cent), and found that the animals drinking the fructose-sweetened liquid altered how the liver metabolised the syrup and, according to the authors, represented a calorie overload to which the body's metabolism was unable to adapt. Laguna and co-workers report that the fructose increased fat synthesis in the liver and also acted on the PPAR-alpha receptor to reduce the degradation of the fructose. PPAR-alpha is said to control fatty acid oxidation. "The most novel finding," said Laguna, "is that this molecular mechanism is related to an impairment in the leptin signal. Leptin is a hormone that plays a key role in the body's energy control; among its peripheral actions, it accelerates fat oxidation in the liver and reduces its synthesis." Rats drinking the fructose-containing beverage were found to have an excess of leptin in blood, which, said the authors, could be related to the degradation of fatty acids in the liver. Leptin resistance is said to affect a transcription factor (Stat-3) that plays a role in the signalling pathway of leptin in the liver and the hypothalamus in the brain. No significant differences in weight between the rats drinking liquids with glucose or fructose were found, said Laguna, "possibly because this was a short-term experiment and there was no time to detect such changes." Work is reported to be on-going with the study of the difference in response to fructose syrup between sexes, the study of the molecular mechanisms of leptin resistance in the liver in rat models, and, further into the future, pilot studies of a fructose-rich diet in humans to find possible markers of metabolic alterations in blood cells. "The fructose in fruit has nothing to do with this study," stressed Laguna. "Fruit is healthy and its consumption is strongly recommended. Our study focuses on liquid fructose intake as an addition to the ordinary diet." Campaigners against the high fructose corn syrup ingredient point to other science showing that the body processes the syrup differently than other sugars due to the fructose content, leading to greater fat storage. However, industry associations and trade bodies, such as the Corn Refiners Association (CRA), have repeatedly claimed there is no scientific evidence to suggest that HFCS is uniquely responsible for people becoming obese. Source: Hepatology Volume 45, Issue 3, Pages 778 - 788 "Impairment of hepatic Stat-3 activation and reduction of PPAR-alpha activity in fructose-fed rats" Authors: N. Roglans, L. Vilà, M. Farré, M. Alegret, R.M. Sánchez, M. Vázquez-Carrera, J.C. Laguna
