Isocaloric restriction normalizes body weight but not relative adiposity, adipose inflammation, or gut microbial diversity in high-fat diet-fed mice

Isocaloric restriction in male C57BL/6 mice normalized final body weight (difference 0.1 g, 95% CI -6.5 to 6.7; P > 0.99) despite persistent relative visceral adiposity.

• Why it matters: Excess energy intake and diet composition may independently shape HFD-driven adiposity, adipose inflammation, and gut microbiome changes, but it is unclear whether restricting calories reverses these effects.
• What they did: Mice (n = 8/group) received LF/LF, HF/HF, HF/IHF, or IHF/IHF for 12 weeks; adiposity, adipose Tnf expression, and fecal 16S rRNA diversity (n = 4/group) were measured.
• The result: Visceral fat relative to body weight stayed higher in IHF/IHF (+1.5 percentage points, 0.04 to 2.9; P = 0.042) and HF/IHF (+1.8, 0.4 to 3.3; P = 0.008), with adipose Tnf remaining elevated in HF/IHF (log2 difference 2.2, 0.2 to 4.2; P = 0.025) and fecal phylogenetic diversity reduced in IHF/IHF (Faith’s PD -3.1, -5.9 to -0.4; P = 0.024).