Research Article Details
| Article ID: | A00764 |
| PMID: | 34977118 |
| Source: | Front Nutr |
| Title: | Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment. |
| Abstract: | Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD. |
| DOI: | 10.3389/fnut.2021.759690 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |