To date, the most studied carotenoids in relation to an antiobesogenic action have been beta-carotene, lycopene, cryptoxanthin, astaxanthin, and fucoxanthin, together with betacarotene-derived retinoids and some other apocarotenoids [7–
9]. Nevertheless, there are more than 600 carotenoids in nature
and many of them, or their derived apocarotenoids, are possibly
capable of interacting with cellular machineries and signaling pathways to elicit beneficial effects against obesity and obesity
comorbidities.
It would be ideal to study carotenoid absorption, metabolism
and contribution to disease prevention through intervention studies in human subjects. However, human studies face specific safety
and ethical issues, they are expensive and often difficult to coordinate, and they do not allow for extensive tissue sampling for mechanistic studies. Because of these limitations, the use of animal
models remains necessary, particularly during the early stages of
research. Unfortunately, no single animal model completely mimics
human absorption and metabolism of carotenoids, and the best
model must be chosen considering the specific application, characteristics of the individual models and the funding and facilities
available [10].
In mammals including humans, two carotenoid metabolizing
enzymes have been identified, denoted as β-carotene-15,15
0 -dioxygenase (BCO1) and β-carotene-9
0 ,10
0 -dioxygenase (BCO2).
BCO1 converts a limited number of provitamin A carotenoids to
retinaldehyde, from which all naturally occurring retinoids can be
synthesized by endogenous pathways. Whereas BCO2 displays
broad substrate specificity and catalyzes oxidative cleavage at the
C9,C10 double bond of a large variety of carotenoids [11] to
generate apo-10
0 -carotenoids (whose biological activity remains
largely unknown). The efficiency of carotenoids intestinal cleavage
varies greatly across species. For instance, adult rats and mice convert almost all absorbed beta-carotene to vitamin A retinoids in the
enterocytes —although they can absorb intact carotenoids, including beta-carotene, when fed diets containing supraphysiological
levels— whereas humans, gerbils, and ferrets incorporate more
beta-carotene into nascent chylomicrons and deliver it to tissues
in its intact form [10]. Thus, the extrapolation of data from rodents
to humans must be done with caution. Nevertheless, rodents have
been widely used in studies of carotenoid activity in mammals, as
they offer advantages over other experimental animal species
[10, 12] (see below). Interestingly, we have previously shown
[13] that, in overt contrast to adult rats, suckling rats partly absorb
dietary beta-carotene intact, even when present at a moderate dose
in the diet, which resembles the situation in humans and suggests
that suckling rats may be an appropriate animal model to study
carotenoids uptake, metabolism and biological activity. In this context, our studies also establish a new potential model for the
Mouse Models to Study Antiobesogenic Effects of Carotenoids
405
9]. Nevertheless, there are more than 600 carotenoids in nature
and many of them, or their derived apocarotenoids, are possibly
capable of interacting with cellular machineries and signaling pathways to elicit beneficial effects against obesity and obesity
comorbidities.
It would be ideal to study carotenoid absorption, metabolism
and contribution to disease prevention through intervention studies in human subjects. However, human studies face specific safety
and ethical issues, they are expensive and often difficult to coordinate, and they do not allow for extensive tissue sampling for mechanistic studies. Because of these limitations, the use of animal
models remains necessary, particularly during the early stages of
research. Unfortunately, no single animal model completely mimics
human absorption and metabolism of carotenoids, and the best
model must be chosen considering the specific application, characteristics of the individual models and the funding and facilities
available [10].
In mammals including humans, two carotenoid metabolizing
enzymes have been identified, denoted as β-carotene-15,15
0 -dioxygenase (BCO1) and β-carotene-9
0 ,10
0 -dioxygenase (BCO2).
BCO1 converts a limited number of provitamin A carotenoids to
retinaldehyde, from which all naturally occurring retinoids can be
synthesized by endogenous pathways. Whereas BCO2 displays
broad substrate specificity and catalyzes oxidative cleavage at the
C9,C10 double bond of a large variety of carotenoids [11] to
generate apo-10
0 -carotenoids (whose biological activity remains
largely unknown). The efficiency of carotenoids intestinal cleavage
varies greatly across species. For instance, adult rats and mice convert almost all absorbed beta-carotene to vitamin A retinoids in the
enterocytes —although they can absorb intact carotenoids, including beta-carotene, when fed diets containing supraphysiological
levels— whereas humans, gerbils, and ferrets incorporate more
beta-carotene into nascent chylomicrons and deliver it to tissues
in its intact form [10]. Thus, the extrapolation of data from rodents
to humans must be done with caution. Nevertheless, rodents have
been widely used in studies of carotenoid activity in mammals, as
they offer advantages over other experimental animal species
[10, 12] (see below). Interestingly, we have previously shown
[13] that, in overt contrast to adult rats, suckling rats partly absorb
dietary beta-carotene intact, even when present at a moderate dose
in the diet, which resembles the situation in humans and suggests
that suckling rats may be an appropriate animal model to study
carotenoids uptake, metabolism and biological activity. In this context, our studies also establish a new potential model for the
Mouse Models to Study Antiobesogenic Effects of Carotenoids
405