Background/Objectives: Fasting-induced elevation of blood ketone body levels suppresses allergic reactions; however, the underlying mechanism remains unclear. This study investigated whether elevated ketone body levels affect allergic contact dermatitis (ACD) and explored nutritional interventions that effectively increase β-hydroxybutyrate (BHB) levels. Additionally, we examined the role of GPR109A, a receptor for β-hydroxybutyrate (BHB), in ketone body-induced allergy suppression through ingestion of a ketogenic substrate. Methods: To evaluate the effects of ketone body precursors, medium-chain triglyceride (MCT) oil or 1,3-butanediol (BD) was administered as a single oral dose (2 g/kg body weight) under fed conditions. Blood BHB concentrations were measured at the time of euthanasia. ACD was induced using 2,4-dinitrofluorobenzene (DNFB), and its severity was assessed by measuring ear swelling and mast cell (MC) degranulation. To determine whether GPR109A mediates ketone body-induced allergy suppression, mepenzolate bromide (MPN), a GPR109A antagonist, was subcutaneously administered before BD treatment. Results: Both MCT oil and BD significantly increased the blood BHB levels. Elevated BHB concentrations were accompanied by reduced ear swelling and MC degranulation in DNFB-treated mice. The anti-allergic effects of BD were abolished by MPN administration, indicating that these effects were mediated by GPR109A activation. Conclusions: Nutritional supplementation with ketogenic substrates, such as MCT oil and BD, may serve as a dietary intervention for ACD by elevating blood BHB levels. GPR109A activation appears to be involved in ketone body-induced allergy suppression, suggesting a mechanistic link between ketone metabolism and immunomodulation.

Background/Objectives: Fasting-induced elevation of blood ketone body levels suppresses allergic reactions; however, the underlying mechanism remains unclear. This study investigated whether elevated ketone body levels affect allergic contact dermatitis (ACD) and explored nutritional interventions that effectively increase β-hydroxybutyrate (BHB) levels. Additionally, we examined the role of GPR109A in ketone body–induced allergy suppression through ingestion of a ketogenic substrate. Methods: To evaluate the effects of ketone body precursors, medium-chain triglyceride (MCT) oil or 1,3-butanediol (BD) was administered as a single oral dose (2 g/kg body weight) under fed conditions. Blood BHB concentrations were measured at the time of euthanasia. ACD was induced using 2,4-dinitrofluorobenzene (DNFB), and its severity was assessed by measuring ear swelling and mast cell (MC) degranulation. To determine whether GPR109A mediates ketone body–induced allergy suppression, mepenzolate bromide (MPN), a GPR109A antagonist, was subcutaneously administered before BD treatment. Results: Both MCT oil and BD significantly increased the blood BHB levels. Elevated BHB concentrations were accompanied by reduced ear swelling and MC degranulation in DNFB-treated mice. The anti-allergic effects of BD were abolished by MPN administration, indicating that these effects were mediated by GPR109A activation. Conclusions: Nutritional supplementation with ketogenic substrates, such as MCT oil and BD, may serve as a dietary intervention for ACD by elevating blood BHB levels. GPR109A activation appears to be involved in ketone body–induced allergy suppression, suggesting a mechanistic link between ketone metabolism and immunomodulation.

Background: Pubertal sucrose intake is a public health concern, but its effects on cholesterol metabolism and male reproductive endocrinology remain poorly understood. Rodent studies of this window have generally used 30% (w/v) sucrose or 20% (w/v) fructose solutions; beverage-like concentrations have been examined less often. Reported effects of dietary sugar on circulating testosterone are inconsistent; we hypothesized that differences in developmental stage might account for this discrepancy. Methods: Male ICR (Institute of Cancer Research) mice had free access to a 10% (w/v) sucrose solution from 4 to 8 weeks of age. We assessed hepatic and plasma lipids, testicular cholesterol and testosterone, hepatic acetyl-CoA carboxylase (ACC) and AMPK phosphorylation, and expression of cholesterol metabolism- and steroidogenesis-related genes. All measurements were performed after a 16 h fast, during which the sucrose solution was replaced with water. Results: Sucrose selectively elevated hepatic and plasma cholesterol without altering triglycerides, the circulating increase being confined to the non-high-density lipoprotein fraction. Phosphorylation of ACC1 and ACC2 rose while AMPK phosphorylation was unchanged. Peritesticular fat weight increased despite unchanged body weight and energy intake. In the testes, cholesterol content and several steroidogenic transcripts increased, whereas steroidogenic enzyme protein was unchanged. Plasma testosterone increased, whereas intratesticular testosterone did not. Conclusions: In male ICR mice, a 10% (w/v) sucrose solution during puberty supplied approximately 25% of total energy intake, with a comparable fall in solid-chow intake; it was associated with a cholesterol-predominant rather than triglyceride-predominant lipid response and higher circulating testosterone. Testicular cholesterol content and plasma testosterone were both higher while steroidogenic enzyme protein was unchanged, indicating an association between the two rather than a change in steroidogenic capacity.

Background: High dietary salt intake has been implicated in immune-mediated inflam-matory diseases; however, its impact on allergic contact dermatitis (ACD) remains unclear. This study examined whether dietary salt exposure during the sensitization phase influ-ences the severity of DNFB-induced ACD in mice. Methods: Female C57BL/6N mice were fed a normal diet (ND) or an 8% high-salt diet (HSD). In a subset, salt intake was normal-ized prior to sensitization (HSD→ND). ACD was induced using a DNFB sensitization and challenge protocol. Ear swelling was quantified using incremental area under the curve (iAUC). Histological analyses and measurements of plasma and skin sodium were per-formed. Results: HSD-fed mice showed greater ear swelling and higher iAUC than ND controls, accompanied by enhanced inflammatory cell infiltration. Skin sodium levels dif-fered among groups, with higher levels in HSD-fed mice compared with the HSD→ND group. Normalization of salt intake prior to sensitization attenuated disease severity. Spearman analyses indicated that total sodium intake and plasma potassium levels were associated with inflammatory severity. Conclusions: Dietary salt exposure during immune sensitization exacerbated experimental ACD and was associated with systemic electrolyte alterations. These findings suggest that sodium exposure during immune activation may influence allergic skin inflammation.

Background: Pubertal sucrose intake is a public health concern, but its effects on cholesterol metabolism and male reproductive endocrinology remain poorly understood. Rodent studies of this window have generally used 30% (w/v) sucrose or 20% (w/v) fructose solutions; beverage-like concentrations have been examined less often. Reported effects of dietary sugar on circulating testosterone are inconsistent; we hypothesized that differences in developmental stage might account for this discrepancy. Methods: Male ICR (Institute of Cancer Research) mice had free access to a 10% (w/v) sucrose solution from 4 to 8 weeks of age. We assessed hepatic and plasma lipids, testicular cholesterol and testosterone, hepatic acetyl-CoA carboxylase (ACC) and AMPK phosphorylation, and expression of cholesterol metabolism- and steroidogenesis-related genes. All measurements were performed after a 16-h fast, during which the sucrose solution was replaced with water. Results: Sucrose selectively elevated hepatic and plasma cholesterol without altering triglycerides, the circulating increase being confined to the non-high-density lipoprotein fraction. Phosphorylation of ACC1 and ACC2 rose while AMPK phosphorylation was unchanged. Peritesticular fat weight increased despite unchanged body weight and energy intake. In the testes, cholesterol content and several steroidogenic transcripts increased, whereas steroidogenic enzyme protein was unchanged. Plasma testosterone increased, whereas intratesticular testosterone did not. Conclusions: In male ICR mice, a 10% (w/v) sucrose solution during puberty supplied approximately 25% of total energy intake, with a comparable fall in solid-chow intake; it was associated with a cholesterol-predominant rather than triglyceride-predominant lipid response and higher circulating testosterone. Testicular cholesterol content and plasma testosterone were both higher while steroidogenic enzyme protein was unchanged, indicating an association between the two rather than a change in steroidogenic capacity.

Background: High dietary salt intake has been implicated in immune-mediated inflammatory diseases; however, its impact on allergic contact dermatitis (ACD) remains unclear. This study examined whether dietary salt exposure during the sensitization phase influences the severity of DNFB-induced ACD in mice. Methods: Female C57BL/6N mice were fed a normal diet (ND) or an 8% high-salt diet (HSD). In a subset, salt intake was normalized prior to sensitization (HSD → ND). ACD was induced using a DNFB sensitization and challenge protocol. Ear swelling was quantified using incremental area under the curve (iAUC). Histological analyses and measurements of plasma and skin sodium were performed. Results: HSD-fed mice showed greater ear swelling and higher iAUC than ND controls, accompanied by enhanced inflammatory cell infiltration. Skin sodium concentration differed among groups, with a higher concentration in HSD-fed mice compared that in the HSD → ND group. Normalization of salt intake prior to sensitization attenuated disease severity. Spearman analyses indicated that total sodium intake and plasma potassium concentration were associated with inflammatory severity. Conclusions: Dietary salt exposure during immune sensitization exacerbated experimental ACD and was associated with systemic electrolyte alterations. These findings suggest that sodium exposure during immune activation may influence allergic skin inflammation.