2. The length of the dietary challenge and the time of its onset
relative to the age of the animals may affect the macroscopic
and molecular obesity-related phenotypes developed. After
only 5 days of a (40%) HFD challenge, an impact on white
adipose tissue global gene expression profile can already be
observed in C57BL/6 J mice [34, 35], which seems to be
highly predictable of the long-term changes observed after
12 weeks of HFD challenge. Nevertheless, for specific white
adipose tissue genes including Pparg2 —a master transcription
factor for adipogenesis and fat tissue metabolism— and some
Pparg2 transcriptional targets a time-dependent response has
been reported [36]. Initially, within the first week of HFD,
these genes are downregulated, which may serve to prevent
excessive fat deposition; after longer periods of HFD (fourth
week onward) they are instead upregulated, which likely contributes to WAT expansion. Moreover, with prolonged HFD,
accumulated oxidative damage in tissues including the liver
may contribute to aggravate metabolic complications, such as
hepatic steatosis [37]. Thus, the duration of the treatment can
be extended up to 24 weeks to see more deleterious effects on
animals, such as the progression of NAFLD [38]. An early
onset of the dietary challenge (e.g., beginning at 4–6 weeks
of age) usually results in a more persistent obese phenotype in
rodents [39].
3. Mouse models deficient for each of the two carotenoiddioxygenases have been established. These genetic models
allow studying the consequences of the accumulation of carotenoids in mammalian tissues in a tunable fashion
[40, 41]. This breakthrough also allows dissecting the effects
of parent carotenoids apart from their eventual apocarotenoidderived signaling products in models (dietary and/or genetic)
of diseases epidemiologically associated with carotenoid intake,
such as obesity.
4. Most rodents tend to become obese on HFD, but there are
variable responses in weight gain, systemic metabolic alterations (i.e., glucose tolerance, insulin resistance, or triglycerides), adipose tissue biology and others parameters depending
on the strain [32]. The C57BL/6 J mice are prone to develop
obesity when fed an HFD, owing to their strain-specific genetic
background, and are one of the most commonly used rodent
strain for the study of diet-induced obesity and its comorbidities [18, 42].
5. As general advice, animal studies should be routinely performed in both female and male animals [43]. Moreover,
sex-dependent differences exist in lipid handling and partitioning between tissues in response to an HFD [44]. Female rats
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Joan Ribot et al.
relative to the age of the animals may affect the macroscopic
and molecular obesity-related phenotypes developed. After
only 5 days of a (40%) HFD challenge, an impact on white
adipose tissue global gene expression profile can already be
observed in C57BL/6 J mice [34, 35], which seems to be
highly predictable of the long-term changes observed after
12 weeks of HFD challenge. Nevertheless, for specific white
adipose tissue genes including Pparg2 —a master transcription
factor for adipogenesis and fat tissue metabolism— and some
Pparg2 transcriptional targets a time-dependent response has
been reported [36]. Initially, within the first week of HFD,
these genes are downregulated, which may serve to prevent
excessive fat deposition; after longer periods of HFD (fourth
week onward) they are instead upregulated, which likely contributes to WAT expansion. Moreover, with prolonged HFD,
accumulated oxidative damage in tissues including the liver
may contribute to aggravate metabolic complications, such as
hepatic steatosis [37]. Thus, the duration of the treatment can
be extended up to 24 weeks to see more deleterious effects on
animals, such as the progression of NAFLD [38]. An early
onset of the dietary challenge (e.g., beginning at 4–6 weeks
of age) usually results in a more persistent obese phenotype in
rodents [39].
3. Mouse models deficient for each of the two carotenoiddioxygenases have been established. These genetic models
allow studying the consequences of the accumulation of carotenoids in mammalian tissues in a tunable fashion
[40, 41]. This breakthrough also allows dissecting the effects
of parent carotenoids apart from their eventual apocarotenoidderived signaling products in models (dietary and/or genetic)
of diseases epidemiologically associated with carotenoid intake,
such as obesity.
4. Most rodents tend to become obese on HFD, but there are
variable responses in weight gain, systemic metabolic alterations (i.e., glucose tolerance, insulin resistance, or triglycerides), adipose tissue biology and others parameters depending
on the strain [32]. The C57BL/6 J mice are prone to develop
obesity when fed an HFD, owing to their strain-specific genetic
background, and are one of the most commonly used rodent
strain for the study of diet-induced obesity and its comorbidities [18, 42].
5. As general advice, animal studies should be routinely performed in both female and male animals [43]. Moreover,
sex-dependent differences exist in lipid handling and partitioning between tissues in response to an HFD [44]. Female rats
412
Joan Ribot et al.