Isocaloric restriction of a high-fat diet under TAK-242 administration: metabolic and gut microbial responses in mice

In male Mus musculus on TAK-242, isocaloric restriction of a high-fat diet did not normalize visceral adiposity, ileal barrier gene expression, or fecal microbial diversity.

• Why it matters: High-fat feeding and energy intake are difficult to disentangle, and prior isocaloric restriction normalized some metabolic measures without restoring gut microbial patterns.
• What they did: Male C57BL/6 mice (n = 8 per group) received low-fat, high-fat ad libitum, or high-fat pair-fed diets for 12 weeks, with TAK-242 (3 ug/g, three times weekly) starting at week 0.4.
• The result: Ad libitum high-fat increased weight gain versus controls (0.48 g/week; group × week P = .012), while pair-feeding lowered fasting glucose; however, microbial community structure was only linked to diet (PERMANOVA P = .022) and did not revert to the low-fat profile.

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