Sargassum has been used as a supplement diet in domestic animals with a hypolipidemic effect. However, Sargassum is a marine alga that bioaccumulates heavy metals. Marine forests of Sargassum liebmannii develop on the Mexican coasts (North Pacific), and it could be employed as a functional food. Nevertheless, it is necessary to prove its safety regarding intake. This study aimed to examine S. liebmannii for chemical composition, heavy-metal quantification, acute and subchronic toxicities, and its antiobesogenic effect. Sargassum liebmannii provides 790.24 kJ (100 g)−1 and it bioaccumulates higher levels of arsenic (11.2165 ± 0.2793 ppm) compared to zinc, nickel, chromium, copper, lead, cadmium, and mercury (0.0059–0.0437 ppm). The acute toxicity was evaluated in C57BL/6J male mice, obtaining LD50 > 10 g kg−1, and it did not produce any sign of toxicity within 7 days of feeding without histological damage in the stomach, intestine, liver, and kidneys. For the subchronic toxicity and antiobesogenic effect, a diet with 20% S. liebmannii was used in Sprague Dawley male rats for 11 weeks. During the study, the animals fed the Sargassum diet did not show toxicity signs, but body weight gain and energy intake were reduced and insulin sensitivity increased. During the end treatment, the adipose tissue decreased 31.5% from the control. The hematology, clinical biochemistry, and the oxidative stress and cellular damage in the stomach, intestine, liver, and kidneys did not show alterations. These results suggest that a S. liebmannii–supplemented diet (Sls-d) is safe and that it has an antiobesogenic effect in rodents.
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