Intake of total fat is linked to obesity and inversely associated with bone density in humans. Epidemiologic and animal studies show that long-chain n-3 (ω-3) PUFAs supplied as fish oil (FO) are beneficial to skeletal health. This study tested the hypothesis that increasing dietary FO would decrease adiposity and improve bone-related outcomes in growing obese mice. Male C57BL/6 mice at 6 wk old were assigned to 6 treatment groups and fed either a normal-fat diet (3.85 kcal/g and 10% energy as fat) or a high-fat diet (HF; 4.73 kcal/g and 45% energy as fat) containing either 0%, 3%, or 9% energy as FO (0FO, 3FO, and 9FO, respectively) ad libitum for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured. The HF diet increased the expression of the adipose tissue tumor necrosis factor α (Tnfa) and serum concentrations of leptin and tartrate-resistant acid phosphatase (TRAP), and decreased serum concentrations of osteocalcin and bone-specific alkaline phosphatase (P < 0.05). FO decreased fat mass (P < 0.05), serum TRAP (P < 0.05), and adipose tissue Tnfa expression (P < 0.01). Bone content of long-chain n-3 PUFAs was increased and n-6 PUFAs were decreased with the elevation in dietary FO content (P < 0.01). Compared with mice fed 9FO, animals fed 3FO had higher femoral bone volume/total volume (25%), trabecular number (23%), connectivity density (82%), and bone mass of second lumbar vertebrae (12%) and lower femoral trabecular separation (-19%). Mice fed the 3FO HF diet had 42% higher bone mass than those fed the 0FO HF diet. These data indicate increasing dietary FO ≤3% energy can decrease adiposity and mitigate HF diet-induced bone deterioration in growing C57BL/6 mice possibly by reducing inflammation and bone resorption. FO at 9% diet energy had no further beneficial effects on bone of obese mice.

Structural differences in dietary fatty acids modify their rate of oxidation and effect on satiety, endpoints that may influence the development of obesity. This study tests the hypothesis that meals containing fat sources with elevated unsaturated fats will result in greater postprandial energy expenditure, fat oxidation, and satiety than meals containing fats with greater saturation. In a randomized, 5-way crossover design, healthy men and women (n = 23; age: 25.7 ± 6.6 years; BMI: 27.7 ± 3.8 kg/m²) consumed liquid meals containing 30 g of fat from heavy cream (HC), olive oil (OO), sunflower oil (SFO), flaxseed oil (FSO), and fish oil (FO). Energy expenditure and diet-induced thermogenesis (DIT) were determined by metabolic rate over a 240 min postprandial period. Serum concentrations of ghrelin, glucose, insulin, and triacylglycerol (TAG) were assessed. DIT induced by SFO was 5% lower than HC and FO (p = 0.04). Energy expenditure and substrate oxidation did not differ between fat sources. Postprandial TAG concentrations were significantly affected by fat source (p = 0.0001). Varying fat sources by the degree of saturation and PUFA type modified DIT but not satiety responses in normal to obese adult men and women.

Leptin is a pleiotropic hormone known for regulating appetite and metabolism. To characterize the role of leptin signaling in rainbow trout, we used CRISPR/Cas9 genome editing to disrupt the leptin receptor (LepR) genes, lepra1 and lepra2. We compared wildtype (WT) and mutant fish that were either fed to satiation or feed deprived for six weeks. The LepR mutants exhibited a hyperphagic phenotype, which led to heavier body weight, faster specific growth rate, increased viscero- and hepatosomatic indices, and greater condition factor. Muscle glycogen, plasma leptin, and leptin transcripts (lepa1) were also elevated in fed LepR mutant fish. Expression levels of several hypothalamic genes involved in feed regulation were analyzed (agrp, npy, orexin, cart-1, cart-2, pomc-a1, pomc-b). No differences were detected between fed WT and mutants except for pomc-b (proopiomelanocortin-b), where levels were 7.5-fold higher in LepR fed mutants, suggesting that pomc-b expression is regulated by leptin signaling. Fatty acid (FA) content did not statistically differ in muscle of fed mutant fish compared to WT. However, fasted mutants exhibited significantly lower muscle FA concentrations, suggesting that LepR mutants exhibit increased FA mobilization during fasting. These data demonstrate a key role for leptin signaling in lipid and energy mobilization in a teleost fish.