White Adipose Tissue Contributes to Cardiac Homeostasis and Adaptation to Cardiometabolic Stress in a Sex- and Depot-Specific Manner

Figures

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  Figure 1. Effects of lipectomy on the mouse body and cardiac morphology. (A) Schematic representation of the experimental design (Created in BioRender. Couet, J. (2026) https://BioRender.com/n6l5lju). Seven-week-old C57BL/6J male (blue) and female (purple) mice were divided into 3 groups. Control mice underwent either a sham surgical procedure (Sham), bilateral ablation of the gonadal visceral fat depots (VAT) or ablation of the inguinal subcutaneous fat depots (SAT). Half of these mice received a standard diet for the following 10 weeks. The MHS (AngII + HFD) group received a standard diet for 4 weeks starting 2 weeks after surgery. (B) Resected visceral or subcutaneous adipose tissue weight, respectively, in male (blue, left) or female (fuchsia, right) animals. (C) Body weight. (D) Tibial length. (E) Indexed heart weight for tibial length (iHeart). (F) Heart weight. (G) Left atrial weight and (H) lungs wet weight. Results are expressed as the mean ± standard error of the mean (SEM)—one-way ANOVA followed by the Holm–Sidak post-test. *: p < 0.05, **: p < 0.01, ***: p < 0.001 and ****: p < 0.0001 between indicated groups (n = 7–8 mice/group).

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  Figure 2. VAT or SAT lipectomy impacts echocardiography parameters in males and females. (A) Relative wall thickness (RWT; LV wall thickness/end-diastolic LV diameter). (B) Corrected LV mass as estimated by echo. (C) Stroke volume. (D) LV ejection fraction (EF; (end-diastolic volume (EDV)−end-systolic volume)/EDV * 100). (E) Left atrial (LA) diameter. (F) E/E’ ratio. (G) E wave. (H) E’ wave. Males: blue and left. Females: fuchsia and right. Results are expressed as mean ± standard error of the mean (SEM)—one-way ANOVA followed by the Holm–Sidak post-test. *: p < 0.05, **: p < 0.01, and ***: p < 0.00 between indicated groups (n = 7–8 mice/group).

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  Figure 3. VAT or SAT lipectomy is associated with sex-dependent modulation of circulating adipokine levels. (A) Adiponectin. (B) Leptin. (C) MCP-1 (monocyte chemoattractant protein 1 or CCL2). Males: blue and left. Females: fuchsia and right. Results are expressed as mean ± standard error of the mean (SEM)—one-way ANOVA followed by the Holm–Sidak post-test. *: p < 0.05, **: p < 0.01, and ****: p < 0.0001 between indicated groups (n = 7–8 mice/group).

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  Figure 4. VAT or SAT lipectomy modulates a large group of LV genes in control male and female mice. (A) Modulation of LV genes associated with cardiomyocyte physiology. (B) LV genes associated with extracellular matrix remodelling. (C) Genes implicated in myocardial energy metabolism. The dotted line in each graph represents the relative expression of the indicated gene in sham-operated mice. Results are expressed as mean ± standard error of the mean (SEM)—Student’s t-test. *: p < 0.05, **: p < 0.01, ***: p < 0.001 and ****: p < 0.0001 between VAT or SAT animals and Sham mice (n = 6–8 mice/group).

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  Figure 5. VAT or SAT lipectomy influence the hypertrophic response of the heart to the MHS in a fat depot- and sex-dependent manner. (A) Indexed heart weight of MHS mice. (B) Ratio of MHS over Ctrl iHeart. (C) LA weight of MHS mice. (D) Ratio of MHS over Ctrl LA weight. The dotted line in graphs (B,D) represents control animals. Males: blue and left. Females: fuchsia and right. Results are expressed as mean ± standard error of the mean (SEM)— one-way ANOVA followed by the Holm–Sidak post-test. *: p < 0.05, **: p < 0.01, and ***: p < 0.001 between indicated groups (n = 7–8 mice/group). Student’s t-test. °: p < 0.05, °°°: p < 0.001 and °°°°: p < 0.0001 between VAT or SAT animals and control (non-MHS) mice.

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  Figure 6. VAT or SAT lipectomy is associated with sex-dependent modulation of adipokine levels in the circulation of MHS mice. (A) Adiponectin. (B) Leptin. (C) MCP-1 (monocyte chemoattractant protein 1 or CCL2). Males: blue and left. Females: fuchsia and right. Results are expressed as mean ± standard error of the mean (SEM)—one-way ANOVA followed by the Holm–Sidak post-test. *: p < 0.05, **: p < 0.01, **: p < 0.001 and ****: p < 0.0001 between indicated groups. °°°: p < 0.001 between MHS and controls. (n = 7–8 mice/group).

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  Figure 7. Ovarian hormone depletion exacerbates pulmonary alterations associated with visceral adipose tissue removal. Lung wet weight (A), lung dry weight (B), and estimated lung water content (C) in ovariectomized (Ovx) females, intact females, and males subjected to sham surgery or visceral adipose tissue (VAT) lipectomy and subsequently exposed to control conditions (Ctrl) or metabolic and hypertensive stress (MHS). Horizontal dashed lines indicate the mean value of the corresponding control group. Box plots represent median, interquartile range, and minimum-to-maximum values; individual data points are shown. Statistical analyses were performed using two-way ANOVA with VAT lipectomy and MHS as factors. Corresponding p values for interaction and main effects are shown below each graph. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. °: p < 0.05, °°: p < 0.01 and °°°°: p < 0.0001 between Ovx groups and corresponding non-Ovx groups. Abbreviations: Ovx, ovariectomized; VAT, visceral adipose tissue; Ctrl, control; MHS, metabolic and hypertensive stress.