Victoria Lee Opalka 11/9/18

The Journal of Internal Medicine (JIM) published this article, “Adverse effects of
fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal
obesity,” in 2017. The authors include: M.R. Taskinen, S. Soderlund, L.H. Bogl, A.
Hakkarainen, N. Matikainen, K.H. Pietilainen, S. Rasanen, N. Lundbom, E. Bjornson, B.
Eliasson, R.M. Mancina, S. Romeo, N. Almeras, G.D. Pepa, C. Vetrani, A. Prinster, G. Annuzzi,
A. Rivellese, J.P. Despres and J. Boren. After researching the authors of this article, they are
from Finland and many of their research topics focus on diabetes, obesity, dyslipidemia,
lipoprotein system and many other propositions.
The purpose of the study was to assess how fructose consumption, seventy-five grams per
day for twelve weeks, affected hepatic lipid metabolism and cardiometabolic risk factors in
seventy-one abdominally obese men (Taskinen et al., 2017, p. 187). This research is important
because Cardiovascular disease (CVD) is the leading cause of mortality worldwide. In fact,
nutrition is a major risk factor of CVD development, such as dietary sugar consumption which is
primarily consumed in sugar-sweetened beverages. These beverages are frequently over
consumed, and research has linked this to nonalcoholic fatty liver disease (NAFLD) (Taskinen et
al., 2017, p. 188). Therefore, determining if the increase risk of cardiometabolic risks and lipid
metabolism is due to a hypercaloric fructose diet or fructose itself is crucial to decrease the
incidence of the fatalities of CVD.
Eighty-one obese men became participants through viewing newspaper advertisements
and volunteering for the study (Taskinen et al., 2017, p. 188). However, after exclusion criteria
was completed, only seventy-one subjects went through the entire study protocol. Each
participant consumed three, 330- mL bottles of lemon carbonated beverages daily during their
habitual meals. Their weight, height and waist circumference were measured at the study center.
In addition, a nutritionist gave participants instructions on filling in a 3-day food records,
whereas a dietitian monitored subjects weight and compliance to the study’s protocol weekly
(Taskinen et al., 2017, p. 189).
Before the fructose intervention, there was four different protocols completed two weeks
prior. These protocols included: oral glucose intolerance test (OGTT), oral fat tolerance test
(OFTT), heparin test and magnetic resonance examinations. These tests were important to
determine how dietary fat was metabolized, liver fat content and subcutaneous fat of the
participants before the fructose intervention period (Taskinen et al., 2017, p. 190). After the
completion of the experimental study, the statistical methods included correlation coefficients
and p-values. A p-value of less than 0.05 was considered statistically significant (Taskinen et al.,
2017, p. 190).
The results of the study conveyed that 75 grams of fructose consumption daily for a
twelve-week period had modest adverse effects on cardiometabolic risk factors. In addition, there
was a significant increase in liver fat with fructose consumption and heaptic de novo lipogenesis
(DNL) (Taskinen et al., 2017, p. 187). According to Sanders & Griffin, “Hepatic DNL is the
biochemical process of synthesizing fatty acids from acetyl-CoA subunits that are produced from
a number of different pathways within the cell, mostly commonly carbohydrate metabolism”
(2016, p. 452). Liver fat increased by approximately ten percent after the fructose intervention
with a p value of 0.001. The changes exhibited by liver fat was also correlated with significant
changes of insulin: p = 0.04 (Taskinen et al., 2017, p. 192). Whereas, there was a significant
decrease in beta-hydroxybutyrate which measures hepatic lipid beta-oxidation (Taskinen et al.,
2017, p. 187). This was indicated by the p value which equaled 0.005 (Taskinen et al., 2017, p.
195).
The mechanisms at play include fructose metabolism and lipogenesis. When fructose is
consumed moderately, fructose is removed from circulation (peripheral blood) via the liver and
there is no fructose beyond the portal vein. Fructose is transported by GLUT5 into the
enterocyte, which has a high affinity for fructose. Next, fructose enters the portal vein via
GLUT2 by facilitated diffusion (Gropper & Smith, 2013, p. 108). However, like mentioned
earlier, the overconsumption of sugar-sweetened beverages has created a range of complications
such as considerable levels of fructose in the peripheral blood. The enzyme fructokinase is found
only in the liver which converts fructose to fructose-1-P (F1P) via phosphorylation (Gropper &
Smith, 2013, p. 108). Fructose can enter as F6P or F1P in glycolysis. However, as F1P, the
enzymes Fructose bisphosphate aldolase cleaves F1P into glyceraldehye-3-phophate (G3P) and
dihydroxyacetone phosphate (DHAP). Due to the entrance of fructose in glycolysis, the
phosphofructokinase regulatory reaction is completely bypassed. This enzyme is allosterically
negatively-modulated by ATP and citrate (Gropper & Smith, 2013, p.108). These products
indicate that the cell is well-fed which stops glycolysis. Since fructose bypasses that regulatory
step, glycolysis continues even if there’s adequate levels of ATP or citrate (Gropper & Smith,
2013, p. 101).
The production of DHAP and G3P follows through the remaining steps of glycolysis. The
net energy formation of glycolysis is 2 ATPs. Therefore, the conversion of fructose to these
three-carbon compounds produces ATP. Since ATP is produced, this activates fatty acid
synthesis and hence, promotes TAG synthesis (Gropper & Smith, 2013, p. 108) After TAG
synthesis in the liver, they are transported by VLDLs (created in the liver) to other parts of the
body (Gropper & Smith, 2013, p. 151). However, with high intakes of fructose and the rate of
lipogenesis, some of these TAGs are not exported out of the liver. Rather, these TAGs are stored
in the hepatic tissue which results in NAFLD (Gropper & Smith, 2013, p. 151). Therefore, a diet
high in carbohydrates suppresses fat oxidation and increases fat synthesis. With a high
carbohydrate intake (fed state), insulin activates Acetyl CoA carboxylase via desphosphorylation
by catalyzing acetyl Co-A to malonyl-CoA to begin fatty acid synthesis (Gropper & Smith, 2013,
p. 172). In addition, insulin inhibits Hormone Sensitive lipase (HSL) that is inside the liver via
dephosphorylation as well. As a result, the amount of fatty acids available for oxidation
decreases (Gropper & Smither, 2013, p. 164).
 References
Gropper, S.S & Smith, J.L. (2013). Advanced Nutrition and Human Metabolism (6th ed).
Belmont, CA: Cengage Learning.
Sanders, F.W.B. & Griffin, J.L. (2016). De novo lipogenesis in the liver in health and disease:
More than just a shunting yard for glucose. Biological reviews of the Cambridge
Philosophical Society, 91(2), 452-68. doi: 10.1111/brv.12178
Taskinen, M.R., Soderlund, S., Bogl, L.H., Hakkarainen, A., Matikainen, N., Pietilainen, K.,
Rasanen, S., Lundom, N., Bjornson, E., Eliasson, B., Mancina, R.M., Romeo, S.,
Almeras, N., Pepa, G.D., Vetrani, C., Prinster, A., Annuzzi, G., Rivellese, A., Depres,
J.P., & Boren, J. (2017). Adverse effects of fructose on cardio metabolic risk factors and
hepatic lipid metabolism in subjects with abdominal Obesity. The Association for the
Publication of the Journal of Internal Medicine, 282, 187-201. doi: 10.1111/joim.12632