Sex differences in the peripubertal response to a short‐term, high‐fat diet intake

Abstract

Obesity is one of the most important health problems facing developed countries because being overweight is associated with a higher incidence of type 2 diabetes, cardiovascular disease and cancer, as well as other comorbidities. Although increased weight gain results from a combination of poor dietary habits and decreased energy expenditure, not all individuals have equal propensities to gain weight or to develop secondary complications of obesity. This is partially a result not only of genetics, including sex, but also the time during which an individual is exposed to an obesogenic environment. In the present study, we have compared the response of male and female mice to short‐term exposure to a high‐fat diet (HFD) or a low‐fat diet during the peripubertal period (starting at 42 days of age) because this is a stage of dramatic hormonal and metabolic modifications. After 1 week on a HFD, there was no significant increase in body weight, although females significantly increased their energy intake. Serum leptin levels increased in both sexes, even though no change in fat mass was detected. Glyceamia and homeostasis model assessment increased in males, suggesting a rapid change in glucose metabolism. Hypothalamic pro‐opiomelanocortin mRNA levels were significantly higher in females on a HFD compared to all other groups, which may be an attempt to reduce their increased energy intake. Hypothalamic inflammation and gliosis have been implicated in the development of secondary complications of obesity; however, no indication of activation of inflammatory processes or gliosis was found in response to 1 week of HFD in the hypothalamus, hippocampus or cerebellum of these young mice. These results indicate that there are both sex and age effects in the response to poor dietary intake because peripubertal male and female mice respond differently to short‐term dietary changes and this response is different from that reported in adult rodents.

Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

“…The age at which mice are placed on an obesogenic diet appears to be a critical determining factor in the development of diet-induced hypothalamic gliosis. Mice which are placed on an obesogenic HFHS diet as juveniles appear to be relatively resistant to the development of hypothalamic gliosis, compared with animals who start the diet later in life ( Freire-Regatillo et al, 2019 ). These differences may be caused by region specific age-related changes in glial function, as functional and transcriptomics studies point to differential activity of metabolic pathways in astrocytes from young compared with older mice ( Clarke et al, 2018 , Santos et al, 2018 ).…”

Modeling Diet‐Induced Metabolic Syndrome in Rodents

“…and reverses if the diet was started in middle-aged mice, where females gain more weight and have a more accentuated impairment in glucose tolerance than males. [42] It is currently widely accepted that sex-based differences influence normal physiological and many pathological functions, and considering sex as a critical biological variable in biomedical research is mandatory to avoid an incomplete understanding of the biological process and harmful sex-dependent effects. [38] Studying how biological sex contributes to our health can help understanding disease etiology, manifestation, progression, and treatment.…”

“…Furthermore, some reports claim that obesity induction is most effective when the diet is started at a young age and continues for several weeks, combining the cumulative effects of diet and the changes in metabolism over the mouse lifespan. [23,42] It is important to highlight that all these statements were made based on studies performed with male mice, which does not seem accurate for female mice. Salinero et al conducted a study to compare the effect of diet-induced obesity on male and female C57BL/6 mice at 6 (juvenile), 9 (young adult), and www.advancedsciencenews.com www.mnf-journal.com M, male; F, female; NI, non-informed; Commercial diets from Research Diets ( a = D12492, b = D12451); CO, control diet; HFD, high fat diet; WD, western diet; GTT, glucose tolerance test; ITT, insulin tolerance test; TC, total cholesterol; TG, triglycerides; LDL, low-density lipoprotein cholesterol; HDL, high-density lipoprotein cholesterol.…”

“…[59,82,83] Finally, it is essential to highlight that the animals' exposure to HFDs can alter many other systems as gut microbiome, inflammatory and neuroinflammatory responses, increase tumorigenesis and risk of cancer, promote behavioral and reproductive disorders, independent of obesity phenotype and major metabolic changes, so researches need to be aware of these alterations. [42,84,85] Considering the complexity of MetS, and visceral obesity as an essential feature of this syndrome, HFDs containing 40-60% of energy from saturated fats, seem to confer more satisfactory outcomes in this context. However, due to the wide variation in the composition of the diets observed among the studies, which can generate high variability, it is extremely relevant to inform in detail the composition of all diets used in the experiments to produce more reliable results allowing comparison between studies.…”

Conflito Entre O Direito À Honra E O Direito À Informação Na Perspectiva Da Responsabilidade Midiática

“…Porém, nem todos os indivíduos têm propensões iguais para ganhar peso ou desenvolver complicações secundárias da obesidade. Isto é parcialmente um resultado não só da genética, incluindo o sexo, mas também do tempo no qual um indivíduo é exposto a um ambiente obesogênico(FREIRE-REGATILLO et al, 2019). A obesidade induzida por DH, dieta composta por 45 a 60% de lipídios, têm demonstrado diferentes efeitos relacionados à idade e tempo de duração de exposição à dieta.…”