Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders

Abstract

Compared with other carbohydrates, fructose-containing caloric sweeteners (sucrose, high-fructose corn syrup, pure fructose and fructose-glucose mixtures) are characterized by: a sweet taste generally associated with a positive hedonic tone; specific intestinal fructose transporters, i.e. GLUT5; a two-step fructose metabolism, consisting of the conversion of fructose carbones into ubiquitous energy substrates in splanchnic organs where fructolytic enzymes are expressed, and secondary delivery of these substrates to extrasplanchnic tissues. Fructose is a dispensable nutrient, yet its energy can be stored very efficiently owing to a rapid induction of intestinal fructose transporters and of splanchnic fructolytic and lipogenic enzymes by dietary fructose-containing caloric sweeteners. In addition, compared with fat or other dietary carbohydrates, fructose may be favored as an energy store because it uses different intestinal absorption mechanisms and different inter-organ trafficking pathways. These specific features make fructose an advantageous energy substrate in wild animals, mainly when consumed before periods of scarcity or high energy turnover such as migrations. These properties of fructose storage are also advantageous to humans who are involved in strenuous sport activities. In subjects with low physical activity, however, these same features of fructose metabolism may have the harmful effect of favoring energy overconsumption. Furthermore, a continuous exposure to high fructose intake associated with a low energy turnover leads to a chronic overproduction of intrahepatic trioses-phosphate production, which is secondarily responsible for the development of hepatic insulin resistance, intrahepatic fat accumulation, and increased blood triglyceride concentrations. In the long term, these effects may contribute to the development of metabolic and cardiovascular diseases.

Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats

“…Although the effect of fructose on weight-gain has often been reported in human studies [28][29][30], it is not always obvious in the animal experimental studies [14,31]. In our experimental conditions, 12 weeks of fructose intake led to IR without influencing the body weight of rats.…”

Fructose and metabolic health: governed by hepatic glycogen status?

“…). Furthermore, free glucose is rarely ingested alone as a sugar and, for this reason, it has been proposed that the ingestion of glucose alone is more reflective of non‐sugar intake from a physiological perspective (Tappy, ). In other words, when referring to sugar intake, we are typically referring to the co‐ingestion of fructose and glucose, and not the ingestion of free glucose alone.…”

“…With regards to hepatic metabolism of carbohydrate, ingestion of glucose in either free form, or as the various polymers such as maltose, maltodextrin and (amylose) starch can be considered physiologically similar stimuli because hydrolysis of glucose polymers is not thought to be rate-limiting to intestinal absorption . Furthermore, free glucose is rarely ingested alone as a sugar and, for this reason, it has been proposed that the ingestion of glucose alone is more reflective of non-sugar intake from a physiological perspective (Tappy, 2018). In other words, when referring to sugar intake, we are typically referring to the co-ingestion of fructose and glucose, and not the ingestion of free glucose alone.…”

Health outcomes of a high fructose intake: the importance of physical activity

“…This set of ‘fructolytic’ enzymes appears to be solely expressed in small bowel enterocytes, hepatocytes and kidney proximal tubular cells (Mayes, ). Interestingly, the same cells also express gluconeogenic and lipogenic enzymes, can release glucose into the blood by the presence of glucose‐6‐phosphatase, and can also release lactate into the systemic circulation (Tappy, ). Hence, fructose metabolism takes place in cells that are also capable of releasing secondary intermediary metabolites into the blood.…”

“…). Interestingly, the membrane transporter GLUT5 and the isoform fructokinase‐A, which are both supposed to be specific for fructose, are present in a wide set of tissues not restricted to the splanchnic region (Tappy, ). Hence, it is also plausible that non‐fructolytic organs metabolize dietary fructose to some extent.…”