A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice

Abstract

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model

“…Simultaneously, LPD decreased the body weight of IR FKO and WT mice, consistent with previous studies 16, 21,29,34,35 . Since LPD reduces body weight in both genotypes and decreases glycemia only in IR FKO mice, we infer that the bene cial effects of LPD on glucose homeostasis are independent of body weight reduction in the IR FKO model.…”

“…In the past decades, the alarming rise in the prevalence of metabolic diseases, including insulin resistance and diabetes, has invigorated interest in developing complementary therapeutic strategies. Reducing dietary proteins has recently been shown to promote or preserve metabolic health in young mice and rats 29,30,33 and obesity-induced metabolic dysfunction rodent models [34][35][36] . This study tested the therapeutic potential of protein restriction (LPD) on a diabetic lipodystrophic mouse model (adipose tissue-speci c insulin receptor knockout, IR FKO ) 22 .…”

“…Most studies conducted so far have demonstrated bene cial metabolic effects at least after 4 weeks of LPD treatment 15,35,43,44 . Unexpectedly, we observed a signi cant reduction in blood glucose as early as 10 days after initiating LPD treatment.…”

The Effects of Fasting or Ketogenic Diet on Endurance Exercise Performance and Metabolism in Female Mice

“…Since dietary intervention can be well controlled in animals, additional studies, particularly in female populations, are warranted to provide definitive conclusions. Consistent with studies in humans [ 30 , 31 , 32 , 33 ] and male rodents [ 41 , 42 , 43 ], we found no benefit of a short-term KD on endurance exercise performance. Several key data may explain this observation.…”

“…Our review of the literature generally found that the KD was not an effective strategy to improve aerobic [ 30 , 31 , 32 , 33 ] or anaerobic [ 34 , 35 , 36 , 37 ] performance in human subjects. However, studies in rodent models were mixed, with observations of enhancements [ 38 , 39 , 40 ], impairments [ 26 ], and no change [ 41 , 42 , 43 ] in exercise performance. Studies in humans present certain limitations, such as controlling dietary intake and obtaining tissue for investigation and molecular insights.…”