Page 52 - Petelin, Ana. 2021. Ed. Zdravje starostnikov / Health of the Elderly. Proceedings. Koper: University of Primorska Press.
P. 52
avje starostnikov | health of the elderly 50 in a positive way, as expression of the genes involved in beta-oxidation CPT1A
and CPT2 was increased, but also in a negative way, since genes involved in the
storage of lipids (DGAT and PLIN2) were upregulated too. These effects, de-
spite some difference, were found for all four studied sweeteners. As expect-
ed, the expression of all genes was higher in the presence of palmitate, which
served as a source of fatty acids. However, the effect of sweeteners alone was
similar also in the environment without added palmitate, where the only fatty
acids in the cells are those endogenously produced from glucose.
On the other hand, a functional assay, showing the total accumulation
of lipids in hepatic cells, did not confirm any major effect of the sweeteners. In
the spectrophotometric analysis of the amount of lipid droplets, we found that
the accumulation remained the same or decreased slightly. It should be noted
that the analysis of gene expression can only give an estimate that the sweeten-
er acts on a certain mechanism, and that overall accumulation of fat is influ-
enced by other pathways that we have not studied. We conclude that the con-
sumption of selected sweeteners, despite the effect on gene expression, does not
affect the increased accumulation of fat in the liver. This is in agreements with
the study of Ma et al. (2015), where NAFLD-related markers were not associat-
ed with the daily intake of drinks containing non-caloric sweeteners. Further,
the investigated sweeteners were found to be non-cytotoxic in tested concen-
trations, which were calculated from a predicted high daily intake and consid-
ering complete absorption, and are thus presumably higher than actual phys-
iologically relevant concentrations. Without a thorough understanding of the
absorption and the metabolism of the sweeteners, accurate concentrations of a
sweetener in the blood stream reaching liver cells in vivo is difficult to predict.
Although many studies describe the effect of sweeteners on NAFLD and
obesity, the mechanisms by which sweeteners affect the human body are not
yet entirely clear. According to Schiffman (2012), too little is known about the
health effects of sweeteners. They propose the need for further studies in nine
different areas, including the need to determine the role of transport mole-
cules in the absorption of sweeteners, the identification of sweetener metab-
olites, metabolic enzymes and potential toxicity of metabolites, the effect of
the sweetener itself on nutrient absorption and weight management, effects of
sweeteners on acute and chronical brain activation, neuroplasticity and taste
receptor interactions in the brain, checking whether sweeteners have clinical-
ly relevant genetic effects, determining long-term effects on the gut microbiota.
Of these, only the cytotoxicity and gene-expression analysis were studied here.
Based on the results obtained, we cannot advise against the use of non-ca-
loric sweeteners as an alternative to sugar for NAFLD prevention and other
health complications. However, in the analysis of gene expression, we observed
significant effects on lipid metabolism that were not previously known. Those
are likely not causally related to the development of NAFLD, but confirm that
sweeteners are not metabolically inert, as was suggested previously by Pepino
(2015) and as such merit further research.
and CPT2 was increased, but also in a negative way, since genes involved in the
storage of lipids (DGAT and PLIN2) were upregulated too. These effects, de-
spite some difference, were found for all four studied sweeteners. As expect-
ed, the expression of all genes was higher in the presence of palmitate, which
served as a source of fatty acids. However, the effect of sweeteners alone was
similar also in the environment without added palmitate, where the only fatty
acids in the cells are those endogenously produced from glucose.
On the other hand, a functional assay, showing the total accumulation
of lipids in hepatic cells, did not confirm any major effect of the sweeteners. In
the spectrophotometric analysis of the amount of lipid droplets, we found that
the accumulation remained the same or decreased slightly. It should be noted
that the analysis of gene expression can only give an estimate that the sweeten-
er acts on a certain mechanism, and that overall accumulation of fat is influ-
enced by other pathways that we have not studied. We conclude that the con-
sumption of selected sweeteners, despite the effect on gene expression, does not
affect the increased accumulation of fat in the liver. This is in agreements with
the study of Ma et al. (2015), where NAFLD-related markers were not associat-
ed with the daily intake of drinks containing non-caloric sweeteners. Further,
the investigated sweeteners were found to be non-cytotoxic in tested concen-
trations, which were calculated from a predicted high daily intake and consid-
ering complete absorption, and are thus presumably higher than actual phys-
iologically relevant concentrations. Without a thorough understanding of the
absorption and the metabolism of the sweeteners, accurate concentrations of a
sweetener in the blood stream reaching liver cells in vivo is difficult to predict.
Although many studies describe the effect of sweeteners on NAFLD and
obesity, the mechanisms by which sweeteners affect the human body are not
yet entirely clear. According to Schiffman (2012), too little is known about the
health effects of sweeteners. They propose the need for further studies in nine
different areas, including the need to determine the role of transport mole-
cules in the absorption of sweeteners, the identification of sweetener metab-
olites, metabolic enzymes and potential toxicity of metabolites, the effect of
the sweetener itself on nutrient absorption and weight management, effects of
sweeteners on acute and chronical brain activation, neuroplasticity and taste
receptor interactions in the brain, checking whether sweeteners have clinical-
ly relevant genetic effects, determining long-term effects on the gut microbiota.
Of these, only the cytotoxicity and gene-expression analysis were studied here.
Based on the results obtained, we cannot advise against the use of non-ca-
loric sweeteners as an alternative to sugar for NAFLD prevention and other
health complications. However, in the analysis of gene expression, we observed
significant effects on lipid metabolism that were not previously known. Those
are likely not causally related to the development of NAFLD, but confirm that
sweeteners are not metabolically inert, as was suggested previously by Pepino
(2015) and as such merit further research.
