Inflammation has been implicated in the pathophysiology of metabolic syndrome and several neurological disorders; evidence is also mounting for long-term aftereffects of inflammation during early brain development. This dissertation project investigated the role of central/peripheral inflammation as a key contributor for the neurological deficits/metabolic dysregulation caused by disparate environmental triggers, including manganese (Mn; metal), lipopolysaccharide (LPS; bacterial infection mimic) or high-fat diet (HFD) in mice. Low-level subchronic Mn drinking water exposure (0.4 g/l) led to increased brain Mn deposition (in a region- and time-independent manner), hyperactivity, and decreased anxiety in adult male mice; the latter effects were accompanied with brain region-specific glial cell activation and altered serotonin (5-HT) homeostasis. Chronic low-grade inflammation caused by repeated peripheral LPS (0.25 mg/kg) administration produced persistent depressive-like behavior and caused region-specific and time-dependent neurochemical alterations in the dopamine (DA), norepinephrine and 5-HT homeostasis in striatum, prefrontal cortex (PFC) and hippocampus of adult male mice. HFD (60 kcal% fat) consumption for 5 weeks by female mice led to hyperactivity and anxiety, whereas mice consuming HFD for 21 weeks did not have locomotor deficits or anxiety-like behavior; after 32 weeks on HFD, the female mice were hypoactive. Mice's short-term object recognition memory remained unaffected regardless of the HFD feeding duration. Peripherally, HFD intake caused persistent glucose intolerance. Compared to age-matched low-fat diet controls, insulin sensitivity was impaired by HFD intake for 5 and 20 weeks, but not for 33 weeks. HFD consumption also caused biphasic (6 and 36 weeks) inflammation, whereas the key lipid metabolism regulatory gene, CD36, was increased at all three time points with the greatest effect at 36 weeks. Maternal HFD consumption increased anxiety in female, but not male adolescent offspring; elevated anxiety was accompanied with altered DA homeostasis in the PFC and the ventral hippocampus. Female offspring of HFD-fed dams treated with a novel anti-inflammatory glycan conjugate showed reduced anxiety. In conclusion, in adults, Mn, LPS, or HFD exposure leads to central and/or peripheral inflammation causing neurological and/or metabolic abnormalities in mice; maternal HFD consumption produces sex-specific behavioral and monoamine alterations in adolescent offspring that are mitigated by an anti-inflammatory intervention.