Intergenerational inheritance induced by a high-fat diet causes hyperphagia and reduced hypothalamic sensitivity to insulin and leptin in the second-generation of rats

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2024-04, Vol.120, p.112333-112333, Article 112333
• Main Authors: Maia, Rosana da Conceição Araújo, Lima, Taynara Carolina, Barbosa, Claudiane Maria, Barbosa, Maria Andréa, de Queiroz, Karina Barbosa, Alzamora, Andréia Carvalho
• Format: Article
• Language: English
• Subjects: Adenine; Adipose tissue; Agouti-related protein; AKT protein; Angiotensin; Angiotensin II; Animals; Appetite; Beta cells; Blood pressure; Body fat; Body mass; Carbohydrates; Carbonyl compounds; Carbonyls; Deoxyribonucleic acid; Diet; DNA; DNA methylation; DNA methyltransferase; DNA methyltransferase enzymes; Enzymes; Epigenetics; Females; Food; Food intake; Gene expression; Glucose; Heredity; High fat diet; Homeostasis; Hyperphagia; Hypothalamus; Insulin; Insulin and leptin sensitivity; Insulin receptors; Insulin resistance; Intergenerational inheritance; Kinases; Metabolism; NAD(P)H oxidase; NADPH oxidase; NADPH-diaphorase; Neuropeptides; Nicotinamide; Nicotinamide adenine dinucleotide; Nutrition research; Offspring; Peptidyl-dipeptidase A; Proteins; Receptors; Satiety; Sensitivity; Signal transduction; Substrates; Superoxide dismutase; Weaning
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2023.112333

•A high-fat diet causes hyperphagia in second-generation offspring.•A high-fat diet induced intergenerational inheritance in second-generation offspring.•A high-fat diet reduced hypothalamic sensitivity to insulin and leptin of second-generation offspring. The aim was to investigate the intergenerational inheritance induced by a high-fat diet on sensitivity to insulin and leptin in the hypothalamic control of satiety in second-generation offspring, which were fed a control diet. Progenitor rats were fed a high-fat or a control diet for 59 d until weaning. The first-generation and second-generation offspring were fed the control diet until 90 d of age. Body mass and adiposity index of the progenitors fed the high-fat diet and the second-generation offspring from progenitors fed the high-fat diet were evaluated as were the gene expression of DNA methyltransferase 3a, angiotensin-converting enzyme type 2, angiotensin II type 2 receptor, insulin and leptin signaling pathway (insulin receptor, leptin receptor, insulin receptor substrate 2, protein kinase B, signal transducer and transcriptional activator 3, pro-opiomelanocortin, and neuropeptide Agouti-related protein), superoxide dismutase activity, and the concentration of carbonyl protein and satiety-regulating neuropeptides, pro-opiomelanocortin and neuropeptide Agouti-related protein, in the hypothalamus. The progenitor group fed a high-fat diet showed increased insulin resistance and reduced insulin-secreting beta-cell function and reduced food intake, without changes in caloric intake. The second-generation offspring from progenitors fed a high-fat diet, compared with second-generation offspring from progenitors fed a control diet group, had decreased insulin-secreting beta-cell function and increased food and caloric intake, insulin resistance, body mass, and adiposity index. Furthermore, second-generation offspring from progenitors fed a high-fat diet had increased DNA methyltransferase 3a, neuropeptide Agouti-related protein, angiotensin II type 1 receptor, and nicotinamide adenine dinucleotide phosphate oxidase p47phox gene expression, superoxide dismutase activity, and neuropeptide Agouti-related protein concentration in the hypothalamus. In addition, there were reduced in gene expression of the insulin receptor, leptin receptor, insulin receptor substrate 2, pro-opiomelanocortin, angiotensin II type 2 receptor, angiotensin-converting enzyme type 2, and angiotensin-(1–7) receptor and pro-opiomelanoc