** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MATERNAL OBESITY (MO) ASSOCIATED WITH THE DEVELOPMENT OF MATERNAL GUT DYSBIOSIS WITH INCREASED GRAM NEGATIVE BACTERIA, INTESTINAL BARRIER DYSFUNCTION RESULTING RELEASE OF LIPOPOLYSACCHARIDE (LPS) FROM A LEAKY GUT, WHICH CAN CAUSE MATERNAL SYSTEMIC INFLAMMATION AND ENHANCE LIPOTOXICITY TO PLACENTA AND FETAL LIVER. OUR PRELIMINARY DATA SHOWED INCREASED LIPID DROPLETS AND TROPHOBLAST APOPTOSIS IN THE PLACENTA OF ANIMALS FED WITH HIGH FAT/HIGH SUCROSE (HFHS) DIET-INDUCED MO. SUPPLEMENTATION OF MACADAMIA NUT-CONTAINING HFHS DIET TO PREGNANT MICE SHOWED DECREASED PROINFLAMMATORY CYTOKINE LEVELS IN THE PLACENTA AND FETAL LIVER COMPARED TO HFHS DIET ALONE FED OBESE PREGNANT MICE. WE ALSO OBSERVED THAT CO-TREATMENT OF TROPHOBLAST WITH PALMITATE AND LPS EXACERBATED PALMITATE-INDUCED TROPHOBLAST LIPOAPOPTOSIS. TREATMENT OF TROPHOBLASTS WITH MONOUNSATURATED FATTY ACIDS (MUFA) DRAMATICALLY PREVENTED PALMITATE-INDUCED TROPHOBLAST LIPOAPOPTOSIS. MUFAS ALSO PREVENTED LPS-INDUCED INFLAMMATION BY BLOCKING INFLAMMASOME ACTIVATION. WE HYPOTHESIZE THAT SUPPLEMENTATION OF MACADAMIA NUTS (CONTAINS HIGH MUFAS, PHYTOSTEROL, AND INSOLUBLE FIBER), AS A WHOLE FOOD APPROACH, PREVENTS MO-INDUCED MATERNAL INTESTINAL BARRIER DYSFUNCTION, AND GUT DYSBIOSIS; LIPOTOXICITY AND INFLAMMATION TO THE PLACENTA AND FETAL LIVER. PROPOSED HYPOTHESIS WILL BE TESTED IN THE FOLLOWING OBJECTIVES: 1) DETERMINE THE PROTECTIVE ROLE OF DIETARY MACADAMIA NUT AGAINST PLACENTAL LIPOTOXICITY AND INFLAMMATION DURING MO; 2) ASCERTAIN THE PROTECTIVE ROLE OF MACADAMIA NUT SUPPLEMENTATION AGAINST MO-INDUCED FETAL FATTY LIVER AND INFLAMMATION; 3) DETERMINE THE PREVENTIVE ROLE OF MACADAMIA NUT AGAINST MATERNAL INTESTINAL BARRIER DYSFUNCTION AND GUT DYSBIOSIS DURING MO. THE PROPOSED OBJECTIVES WILL CONTRIBUTE TO THE MECHANISTIC INSIGHTS ON THE WHOLE FOOD-DERIVED BIOACTIVE COMPONENTS PRESENT IN THE MACADAMIA NUT TO PREVENT MO-INDUCED COMPLICATIONS.