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. 2025 Aug 18:16:1592317.
doi: 10.3389/fphys.2025.1592317. eCollection 2025.

Leptin's crucial modulatory role in regulating body mass homeostasis of high-fat-fed striped field mice (Apodemus agrarius)

Yue Ren  1   2 , Guangtong Guo  1 , Yu Hou  1   2 , Kuiyou Chen  1 , Xinsheng Pu  1 , Mengfan Tao  1 , Yunlong Ren  1 , Xin'gen Yang  1   2
Affiliations

Leptin's crucial modulatory role in regulating body mass homeostasis of high-fat-fed striped field mice (Apodemus agrarius)

Yue Ren et al. Front Physiol. .

Abstract

To investigate into the role of leptin in body mass in high-fat-fed animals. Male striped field mice (Apodemus agrarius) fed high-fat diets were given leptin (0.5 μg/g.d) via intraperitoneal injection for 28 days. Their body mass, digestive metrics, and physiological parameters of food consumption and energy metabolism were compared to those of the control and high-fat food groups. Firstly, the high-fat diet did not cause weight gain in Apodemus agrarius, and the animals on the diet ate less and had higher apparent digestibility. Furthermore, exogenous leptin injection in A. agrarius reduced food intake, increased fecal content, and reduced apparent digestibility. Additionally, exogenous leptin injection inhibited the activity of the AMPK in the hypothalamus, increased the activity of malonyl CoA, inhibited the expression of orexigenic neuropeptide mRNA, promoted the expression of anorexigenic neuropeptide mRNA, and thus reduced food intake and body mass. Finally, exogenous leptin injection increased uncoupling protein 1 content, T45'-deiodinase II activity, and cytochrome C oxidase activity in brown adipose tissue, increased serum triiodothyronine, and increased animal energy consumption. In conclusion, our data indicate that leptin affects body mass in animals on a high-fat diet in two ways: by inhibiting food intake and increasing energy expenditure.

Keywords: AMPK; Apodemus agrarius; body mass; high-fat food; leptin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Changes in body mass of male striped field mice. Significant differences within group were indicated by different alphabetic letters. And significant between groups differences were indicated by *, and * as significant, P < 0.05, ** as extremely significant, P < 0.01. Significant differences in HFD-leptin group were indicated by different lowercase letter. Data are presented as mean ± SEM.
FIGURE 2
FIGURE 2
Effect of leptin on food intake (A), daily fecal output (B), net food intake (C), and apparent digestibility (D). Significant differences within group were indicated by different alphabetic letters. And significant between groups differences were indicated by *, and * as significant, P < 0.05, ** as extremely significant, P < 0.01. Significant differences in HFD and HFD-Leptin group were indicated by different capital letter and lowercase letter, respectively. Data are presented as mean ± SEM.
FIGURE 3
FIGURE 3
Effect of leptin on serum hormone levels in Apodemus agrarius fed high fat diet. The changes of serum hormone (A). The change of leptin on WAT (B), and correlation analysis between leptin and serum hormone (C). Adiponectin Significant group differences were indicated by different alphabetic letters, P < 0.05.
FIGURE 4
FIGURE 4
Leptin receptor (A), activity of AMPK (B), malonyl CoA (C), as well as expression of hypothalamus neuropeptidesm mRNA (D) in Apodemus agrarius, and correlation heat map (E). Significant group differences were indicated by different alphabetic letters, P < 0.05.
FIGURE 5
FIGURE 5
Effect of leptin on protein content and enzyme activity in BAT. Leptin affects UCP1 content (A), T45′-DII activity (B) and COX activity (C) in BAT of Apodemus agrarius. And correlation analysis between serum hormone and protein content as well as enzyme activity in BAT (D). Significant group differences were indicated by different alphabetic letters, P < 0.05.
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